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NK Cells Armed with Chimeric Antigen Receptors (CAR): Roadblocks to Successful Development

CELLS (2021)

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CXCR4 and anti-BCMA CAR co-modified natural killer cells suppress multiple myeloma progression in a xenograft mouse model

Yu Yang Ng et al.

Summary: The study demonstrates that the co-expression of CXCR4 and anti-BCMA CAR on NK cells is an effective way to control MM progression by enhancing NK cell infiltration into the bone marrow and reducing tumor burden, leading to prolonged survival of patients.

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Summary: Optimizing synthetic nanocarriers is a challenging process that involves strategies similar to chemical evolution. Libraries of nanocarriers are generated through combinatorial chemistry or variation and combination of known functional elements, with screening in appropriate test systems providing delivery candidates and a refined understanding of cellular delivery mechanisms. Rational design and computational algorithms are also used to further optimize candidates into nanocarriers with improved safety and efficacy.

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Targeting a cytokine checkpoint enhances the fitness of armored cord blood CAR-NK cells

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Summary: The study combined targeting of CIS protein with CAR engineering of NK cells, leading to improved NK cell effector function and successful antitumor activity in a lymphoma mouse model. This approach represents a promising milestone in the development of next-generation NK cells for cancer immunotherapy.

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Chimeric antigen receptor (CAR) natural killer (NK)-cell therapy: leveraging the power of innate immunity

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Summary: CAR T cells are an emerging cancer treatment with limitations including toxicity, manufacturing complexity, and cost. NK cells have potential as a safer and more accessible source for CAR therapy, and genetic engineering of NK cells to express CAR is showing promising results in preclinical studies and clinical trials.

BRITISH JOURNAL OF HAEMATOLOGY (2021)

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Summary: NK cells are a unique type of innate lymphoid cells with therapeutic potential in cancer immunotherapy. They can be obtained from various sources and expanded ex vivo for therapeutic use. Developing ex vivo NK cell expansion techniques can lead to higher cell doses and application of genetic engineering methods.

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Opportunities for innovation: Building on the success of lipid nanoparticle vaccines

Jessica Huang et al.

Summary: Lipid nanoparticle (LNP) formulations of messenger RNA (mRNA) have shown high efficacy as vaccines against SARS-CoV-2, highlighting their potential as a delivery system for next generation biological therapies. Key considerations for engineering LNPs as a vaccine delivery system include improving mRNA protection, optimizing cytosolic delivery, targeting specific cells, minimizing side effects, and controlling RNA release. Innovations in LNP vaccines are likely to accelerate with recent successes, with implications for a wide range of therapeutic applications beyond vaccination such as gene therapy.

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A robust platform for expansion and genome editing of primary human natural killer cells

Rih-Sheng Huang et al.

Summary: This work presents an integrated platform for streamlined expansion and nonviral gene editing of cryopreserved primary human NK cells using CRISPR-Cas9 ribonucleoproteins. The optimized Cas9 nucleofection protocol allows efficient multiplex gene knockout in NK cells while maintaining high cell viability and minimal off-target effects. Introduction of a DNA template also enables in-frame gene knock-in across multiple loci, demonstrating the advantages and flexibility of using cryopreserved NK cells as potential off-the-shelf engineered therapeutic agents.

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Engineering NK Cells for CAR Therapy-Recent Advances in Gene Transfer Methodology

Paula Schmidt et al.

Summary: The development of CAR-NK cells allows for harnessing the innate anti-tumor ability of NK cells against target tumor antigens, with the potential for creating an off-the-shelf therapeutic product applicable to most patients.

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The Influence of Chimeric Antigen Receptor Structural Domains on Clinical Outcomes and Associated Toxicities

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Summary: CAR-T cell therapy has significantly improved the prognosis of patients with B cell malignancies, but severe treatment-related toxicities remain a challenge. This review of 17 clinical trials of anti-CD19 CAR-T cell therapies highlights the association of the CD28 structural hinge and transmembrane CAR domains with both clinical efficacy and severe toxicity. Further investigation into structural CAR domains is recommended for improved CAR design and safer therapies.

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Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma

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Summary: The phase 2 study confirmed the efficacy and safety of ide-cel in patients with relapsed and refractory myeloma, with a majority of patients achieving responses and 26% achieving MRD-negative status. Despite the high response rate, almost all patients experienced grade 3 or 4 toxic effects, including hematologic toxic effects and cytokine release syndrome.

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Modifications to the Framework Regions Eliminate Chimeric Antigen Receptor Tonic Signaling

Elisa Landoni et al.

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Development of CAR T-cell lymphoma in 2 of 10 patients effectively treated with piggyBac-modified CD19 CAR T cells

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CARAMBA: a first-in-human clinical trial with SLAMF7 CAR-T cells prepared by virus-free Sleeping Beauty gene transfer to treat multiple myeloma

Sabrina Prommersberger et al.

Summary: Clinical development of CAR-T-cell therapy has been advanced by synthetic biology, genetic engineering, and clinical-grade manufacturing, with the goal of providing safe, effective, and economically sustainable treatment. The CARAMBA project aims to demonstrate virus-free CAR gene transfer using advanced SB transposon technology, potentially improving vector procurement, CAR-T manufacturing, and distribution. The project focuses on utilizing SB-based CAR-T cells targeting the SLAMF7 antigen in multiple myeloma, with promising preclinical results indicating potent anti-myeloma activity.

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Summary: Gene therapy can be used to treat monogenic disorders or enhance cells with new abilities. German research institutions have made significant contributions to the development of gene therapy, including designing vectors, conducting clinical trials, and assessing vector efficacy and safety.

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CAR-T cell therapy: current limitations and potential strategies

Robert C. Sterner et al.

Summary: CAR-T cell therapy has shown remarkable clinical responses in certain subsets of leukemia or lymphoma, but faces challenges in solid tumors and hematological malignancies. Innovative strategies and approaches are necessary to overcome these challenges and improve the efficacy of CAR-T cells.

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Lin Xia et al.

Summary: The study revealed that immunosuppressive genes induced by EGFR CAR T cells were sensitive to a CDK7 inhibitor THZ1, which can overcome resistance in TNBC tumors. Combination therapy with THZ1 and EGFR CAR T cells suppressed immune resistance, tumor growth, and metastasis in TNBC tumor models. This suggests that transcriptional modulation using epigenetic inhibitors could offer a potential avenue for treating TNBC in the clinic.

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GD2 redirected CAR T and activated NK-cell-mediated secretion of IFNγ overcomes MYCN-dependent IDO1 inhibition, contributing to neuroblastoma cell immune escape

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Retargeting of NK-92 Cells against High-Risk Rhabdomyosarcomas by Means of an ERBB2 (HER2/Neu)-Specific Chimeric Antigen Receptor

Leonie D. H. Gossel et al.

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Freddie Bray et al.

Summary: CVD and cancer are now leading causes of premature death in 127 countries with cancer poised to overtake CVD in most countries over the course of this century. Governments must consider these transitions in disease profiles when developing cancer policies at the local level.

CANCER (2021)

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Review Immunology

Chimeric antigen receptor- and natural killer cell receptor-engineered innate killer cells in cancer immunotherapy

Cai Zhang et al.

Summary: IKCs, particularly NK cells, NKT cells, and gamma delta T cells, exhibit specific tumor recognition and potent antitumor functions, with low risk of developing GVHD, making them potentially excellent candidates for cancer immunotherapy. Advances in synthetic biology and genetic engineering techniques will further optimize IKC-based anticancer therapies.

CELLULAR & MOLECULAR IMMUNOLOGY (2021)

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Therapeutic Targeting of Mesothelin with Chimeric Antigen Receptor T Cells in Acute Myeloid Leukemia

Quy Le et al.

Summary: The study showed that MSLN is a viable target for CAR T-cell therapy in AML and that inhibiting MSLN shedding can improve CAR T-cell efficacy. MSLN is expressed on the cell surface of AML blasts and leukemic stem cell-enriched subset, but not on normal hematopoietic stem and progenitor cells. MSLN CAR T cells are highly effective in eliminating MSLN-positive AML cells without impacting normal HSPCs.

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CAR T-Cell Therapy in Hematological Malignancies

Theresa Haslauer et al.

Summary: CAR T-cells are a promising therapeutic approach for hematological malignancies, particularly in lymphoma and acute lymphocytic leukemia. Despite encouraging clinical results, challenges remain in treating other hematological malignancies.

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Phase I clinical trial of EGFR-specific CAR-T cells generated by the piggyBac transposon system in advanced relapsed/refractory non-small cell lung cancer patients

Yajun Zhang et al.

Summary: This Phase I clinical trial demonstrated that the non-viral piggyBac transposon system-engineered EGFR-CAR T-cell therapy is safe and feasible in treating EGFR-positive advanced relapsed/refractory NSCLC patients. The therapy was well tolerated by all nine patients, with one patient showing a partial response lasting over 13 months. The progression-free survival was 7.13 months and the median overall survival was 15.63 months for these patients.

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CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial

Jay Y. Spiegel et al.

Summary: Despite impressive progress in CAR-T cell therapy, more than 50% of patients treated with CD19-targeting CAR-T cells experience disease progression, often associated with antigen loss. To address this issue, researchers tested a bispecific CAR targeting CD19 and/or CD22, which showed high efficacy in preventing relapse in patients with B-ALL and LBCL. Antigen loss was identified as a major cause of CAR T cell resistance, emphasizing the importance of engineering multi-specific CAR T cells with equivalent potency and cytokine production as a quality indicator for potency.

NATURE MEDICINE (2021)

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Improved Activity against Acute Myeloid Leukemia with Chimeric Antigen Receptor (CAR)-NK-92 Cells Designed to Target CD123

Michael A. Morgan et al.

Summary: Engineering immune cells to express chimeric antigen receptors (CARs) targeting CD123 using alpharetroviral vectors enhances anti-AML activity, with IL-15 expression being crucial for in vivo persistence of CAR-NK cells. This approach supports further research on anti-CD123-CAR-NK cells for AML therapy and suggests potential strategies to optimize CAR-NK anti-AML efficacy.

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Progress in Treatment of Non-Small Cell Lung Cancer Harboring HER2 Aberrations

Jun Ni et al.

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NKG2D-CAR-transduced natural killer cells efficiently target multiple myeloma

Alejandra Leivas et al.

Summary: CAR-T-cell therapy has shown promising results against multiple myeloma, but with serious toxicities, while CAR-NK cells may have less toxicity against resistant myeloma cells. By using receptors like NKG2D, CAR-NK cells can exhibit broad target specificity. The study demonstrates the effective modification of autologous NKAE cells from MM patients to safely express a NKG2D-CAR, showing enhanced antimyeloma activity and supporting the development of NKG2D-CAR-NK-cell therapy for MM.

BLOOD CANCER JOURNAL (2021)

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A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti-PD-1 Agent Pembrolizumab

Prasad S. Adusumilli et al.

Summary: Regional delivery of mesothelin-targeted CAR T-cell therapy followed by pembrolizumab administration is safe, feasible, and demonstrates evidence of antitumor efficacy in patients with malignant pleural diseases. Our data support the investigation of combination immunotherapy with CAR T cells and PD-1 blockade agents in solid tumors.

CANCER DISCOVERY (2021)

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Nonviral genome engineering of natural killer cells

Gabrielle M. Robbins et al.

Summary: NK cells have the potential to be a crucial part of cancer immunotherapy, but face challenges such as in vivo persistence and the tumor microenvironment. Enhancing NK cell resistance to tumor inhibitory signaling through genome engineering may improve their efficacy in cancer treatment.

STEM CELL RESEARCH & THERAPY (2021)

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Expanded human NK cells armed with CAR uncouple potent anti-tumor activity from off-tumor toxicity against solid tumors

Ana L. Portillo et al.

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Bihui Cao et al.

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Jianfeng Zhao et al.

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Article Genetics & Heredity

Design and analysis of stably integrated reporters for inducible transgene expression in human T cells and CAR NK-cell lines

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BMC MEDICAL GENOMICS (2019)

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Article Oncology

Genetically engineered CAR NK cells display selective cytotoxicity against FLT3-positive B-ALL and inhibit in vivo leukemia growth

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INTERNATIONAL JOURNAL OF CANCER (2019)

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Article Biotechnology & Applied Microbiology

Adoptive Transfer of NKG2D CAR mRNA-Engineered Natural Killer Cells in Colorectal Cancer Patients

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MOLECULAR THERAPY (2019)

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Article Oncology

Radiochemotherapy combined with NK cell transfer followed by second-line PD-1 inhibition in apatient with NSCLC stage IIIb inducing long-term tumor control: acase study

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STRAHLENTHERAPIE UND ONKOLOGIE (2019)

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Review Biochemistry & Molecular Biology

The role of cytokines in the regulation of NK cells in the tumor environment

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CYTOKINE (2019)

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2B4 costimulatory domain enhancing cytotoxic ability of anti-CD5 chimeric antigen receptor engineered natural killer cells against T cell malignancies

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JOURNAL OF HEMATOLOGY & ONCOLOGY (2019)

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Review Cell Biology

Mechanisms of natural killer cell-mediated cellular cytotoxicity

Isabel Prager et al.

JOURNAL OF LEUKOCYTE BIOLOGY (2019)

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Review Cell Biology

Limitations in the Design of Chimeric Antigen Receptors for Cancer Therapy

Stefan Stoiber et al.

CELLS (2019)

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Review Immunology

Genetic reprogramming for NK cell cancer immunotherapy with CRISPR/Cas9

Lukman O. Afolabi et al.

IMMUNOLOGY (2019)

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Article Oncology

Anti-αFR CAR-engineered NK-92 Cells Display Potent Cytotoxicity Against αFR-positive Ovarian Cancer

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JOURNAL OF IMMUNOTHERAPY (2019)

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Article Oncology

Construction of chimeric antigen receptor-modified T cells targeting EpCAM and assessment of their anti-tumor effect on cancer cells

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MOLECULAR MEDICINE REPORTS (2019)

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Article Oncology

Development of c-MET-specific chimeric antigen receptor-engineered natural killer cells with cytotoxic effects on human liver cancer HepG2 cells

Bing Liu et al.

MOLECULAR MEDICINE REPORTS (2019)

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Review Cell & Tissue Engineering

Solid Tumors Challenges and New Insights of CAR T Cell Engineering

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STEM CELL REVIEWS AND REPORTS (2019)

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Article Immunology

Human CAR NK Cells: A New Non-viral Method Allowing High Efficient Transfection and Strong Tumor Cell Killing

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FRONTIERS IN IMMUNOLOGY (2019)

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Review Immunology

A Comparison of Plasmid DNA and mRNA as Vaccine Technologies

Margaret A. Liu

VACCINES (2019)

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Review Biochemistry & Molecular Biology

Gangliosides: The Double-Edge Sword of Neuro-Ectodermal Derived Tumors

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Article Biochemistry & Molecular Biology

Polymeric Carriers for Nucleic Acid Delivery: Current Designs and Future Directions

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BIOMACROMOLECULES (2019)

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NKT Cells Coexpressing a GD2-Specific Chimeric Antigen Receptor and IL15 Show Enhanced In Vivo Persistence and Antitumor Activity against Neuroblastoma

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CLINICAL CANCER RESEARCH (2019)

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Article Biochemistry & Molecular Biology

Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR

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Article Immunology

A Distinct Subset of Highly Proliferative and Lentiviral Vector (LV)-Transducible NK Cells Define a Readily Engineered Subset for Adoptive Cellular Therapy

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Multifunctional nanoparticles for genetic engineering and bioimaging of natural killer (NK) cell therapeutics

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BIOMATERIALS (2019)

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A highly soluble Sleeping Beauty transposase improves control of gene insertion

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NATURE BIOTECHNOLOGY (2019)

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Engraftment of mesothelin chimeric antigen receptor using a hybrid Sleeping Beauty/minicircle vector into NK-92MI cells for treatment of pancreatic cancer

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Review Immunology

Mechanisms of Relapse After CD19 CAR T-Cell Therapy for Acute Lymphoblastic Leukemia and Its Prevention and Treatment Strategies

Xinjie Xu et al.

FRONTIERS IN IMMUNOLOGY (2019)

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Review Oncology

Teaching an old dog new tricks: next-generation CAR T cells

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BRITISH JOURNAL OF CANCER (2019)

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Review Oncology

Advances in HER2-Targeted Therapy: Novel Agents and Opportunities Beyond Breast and Gastric Cancer

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CLINICAL CANCER RESEARCH (2019)

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Safety and Tolerability of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors in Oncology

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DRUG SAFETY (2019)

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Article Immunology

Efficient and Robust NK-Cell Transduction With Baboon Envelope Pseudotyped Lentivector

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Article Oncology

Activated Natural Killer Cells in Combination with Anti-GD2 Antibody Dinutuximab Improve Survival of Mice after Surgical Resection of Primary Neuroblastoma

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CLINICAL CANCER RESEARCH (2019)

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Mesothelin as a biomarker for targeted therapy

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BIOMARKER RESEARCH (2019)

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Article Oncology

Preclinical Targeting of Human Acute Myeloid Leukemia Using CD4-specific Chimeric Antigen Receptor (CAR) T Cells and NK Cells

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JOURNAL OF CANCER (2019)

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Article Immunology

Ex vivo Hsp70-Activated NK Cells in Combination With PD-1 Inhibition Significantly Increase Overall Survival in Preclinical Models of Glioblastoma and Lung Cancer

Maxim Shevtsov et al.

FRONTIERS IN IMMUNOLOGY (2019)

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Article Oncology

Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity

E. Liu et al.

LEUKEMIA (2018)

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Article Oncology

Reversible Transgene Expression Reduces Fratricide and Permits 4-1BB Costimulation of CAR T Cells Directed to T-cell Malignancies

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CANCER IMMUNOLOGY RESEARCH (2018)

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Article Cell & Tissue Engineering

Human iPSC-Derived Natural Killer Cells Engineered with Chimeric Antigen Receptors Enhance Anti-tumor Activity

Ye Li et al.

CELL STEM CELL (2018)

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Article Dermatology

The siRNA-mediated downregulation of PD-1 alone or simultaneously with CTLA-4 shows enhanced in vitro CAR-T-cell functionality for further clinical development towards the potential use in immunotherapy of melanoma

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EXPERIMENTAL DERMATOLOGY (2018)

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Article Biotechnology & Applied Microbiology

Preclinical Efficacy and Safety of CD19CAR Cytokine-Induced Killer Cells Transfected with Sleeping Beauty Transposon for the Treatment of Acute Lymphoblastic Leukemia

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HUMAN GENE THERAPY (2018)

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Review Oncology

Clinical use of lentiviral vectors

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LEUKEMIA (2018)

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Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia

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The development of CAR design for tumor CAR-T cell therapy

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Oncotarget (2018)

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Novel Human NK Cell Line Carrying CAR Targeting EGFRvIII Induces Antitumor Effects in Glioblastoma Cells

Toshiharu Murakami et al.

ANTICANCER RESEARCH (2018)

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Article Immunology

Pharmacologically upregulated carcinoembryonic antigen-expression enhances the cytolytic activity of genetically-modified chimeric antigen receptor NK-92MI against colorectal cancer cells

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BMC IMMUNOLOGY (2018)

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Article Oncology

Preclinical Evaluation of the Hsp70 Peptide Tracer TPP-PEG24-DFO[89Zr] for Tumor-Specific PET/CT Imaging

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CANCER RESEARCH (2018)

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Article Immunology

CRISPR/Cas9 and CAR-T cell, collaboration of two revolutionary technologies in cancer immunotherapy, an instruction for successful cancer treatment

Hasan Mollanoori et al.

HUMAN IMMUNOLOGY (2018)

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Article Multidisciplinary Sciences

Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells

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NATURE (2018)

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Review Immunology

Viral and Nonviral Engineering of Natural Killer Cells as Emerging Adoptive Cancer Immunotherapies

Sandro Matosevic

JOURNAL OF IMMUNOLOGY RESEARCH (2018)

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Review Immunology

Natural Killer Cells: Development, Maturation, and Clinical Utilization

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FRONTIERS IN IMMUNOLOGY (2018)

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Cell engineering with microfluidic squeezing preserves functionality of primary immune cells in vivo

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

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Article Immunology

Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models

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JOURNAL OF IMMUNOLOGY RESEARCH (2018)

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Article Oncology

Purinergic targeting enhances immunotherapy of CD73(+) solid tumors with piggyBac-engineered chimeric antigen receptor natural killer cells

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JOURNAL FOR IMMUNOTHERAPY OF CANCER (2018)

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Article Medicine, Research & Experimental

Pancreatic cancer therapy with combined mesothelin-redirected chimeric antigen receptor T cells and cytokine-armed oncolytic adenoviruses

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JCI INSIGHT (2018)

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Meeting Abstract Hematology

CD19 Redirected CAR NK Cells Are Equally Effective but Less Toxic Than CAR T Cells

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BLOOD (2018)

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Article Oncology

Enhanced CAR T-cell engineering using non-viral Sleeping Beauty transposition from minicircle vectors

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LEUKEMIA (2017)

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Article Oncology

Targeting Ewing sarcoma with activated and GD2-specific chimeric antigen receptor-engineered human NK cells induces upregulation of immune-inhibitory HLA-G

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ONCOIMMUNOLOGY (2017)

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Article Biotechnology & Applied Microbiology

Minicircle Versus Plasmid DNA Delivery by Receptor-Targeted Polyplexes

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HUMAN GENE THERAPY (2017)

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Article Biotechnology & Applied Microbiology

Optimization of Human NK Cell Manufacturing: Fully Automated Separation, Improved Ex Vivo Expansion Using IL-21 with Autologous Feeder Cells, and Generation of Anti-CD123-CAR-Expressing Effector Cells

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HUMAN GENE THERAPY (2017)

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Article Biochemical Research Methods

Retroviral gene transfer into primary human NK cells activated by IL-2 and K562 feeder cells expressing membrane-bound IL-21

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JOURNAL OF IMMUNOLOGICAL METHODS (2017)

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Article Biotechnology & Applied Microbiology

Adenovirotherapy Delivering Cytokine and Checkpoint Inhibitor Augments CAR T Cells against Metastatic Head and Neck Cancer

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MOLECULAR THERAPY (2017)

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Article Biotechnology & Applied Microbiology

Function of Novel Anti-CD19 Chimeric Antigen Receptors with Human Variable Regions Is Affected by Hinge and Transmembrane Domains

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MOLECULAR THERAPY (2017)

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Review Biotechnology & Applied Microbiology

Quantitative Imaging Approaches to Study the CAR Immunological Synapse

Malini Mukherjee et al.

MOLECULAR THERAPY (2017)

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Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection

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NATURE (2017)

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Article Nanoscience & Nanotechnology

In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers

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NATURE NANOTECHNOLOGY (2017)

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Article Cell Biology

A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma

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Article Multidisciplinary Sciences

Hit-and-run programming of therapeutic cytoreagents using mRNA nanocarriers

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NATURE COMMUNICATIONS (2017)

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Review Oncology

Driving better and safer HER2-specific CARs for cancer therapy

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ONCOTARGET (2017)

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Article Immunology

Synergistic Effects of Cabozantinib and EGFR-Specific CAR-NK-92 Cells in Renal Cell Carcinoma

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JOURNAL OF IMMUNOLOGY RESEARCH (2017)

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Article Oncology

Romidepsin alone or in combination with anti-CD20 chimeric antigen receptor expanded natural killer cells targeting Burkitt lymphoma in vitro and in immunodeficient mice

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ONCOIMMUNOLOGY (2017)

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Review Biochemistry & Molecular Biology

Preclinical and clinical advances in transposon-based gene therapy

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BIOSCIENCE REPORTS (2017)

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Article Cell & Tissue Engineering

Continuously expanding CAR NK-92 cells display selective cytotoxicity against B-cell leukemia and lymphoma

Sarah Oelsner et al.

CYTOTHERAPY (2017)

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Article Genetics & Heredity

Efficient generation of gene-modified human natural killer cells via alpharetroviral vectors

Julia D. Suerth et al.

JOURNAL OF MOLECULAR MEDICINE-JMM (2016)

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Article Oncology

ErbB2/HER2-Specific NK Cells for Targeted Therapy of Glioblastoma

Congcong Zhang et al.

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE (2016)

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Article Oncology

ErbB2/HER2-Specific NK Cells for Targeted Therapy of Glioblastoma

Congcong Zhang et al.

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE (2016)

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Article Oncology

Dual targeting of glioblastoma with chimeric antigen receptor-engineered natural killer cells overcomes heterogeneity of target antigen expression and enhances antitumor activity and survival

Sabrina Genssler et al.

ONCOIMMUNOLOGY (2016)

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Article Cell Biology

CD19-CAR engineered NK-92 cells are sufficient to overcome NK cell resistance in B-cell malignancies

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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (2016)

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Article Medicine, Research & Experimental

Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells

Partow Kebriaei et al.

JOURNAL OF CLINICAL INVESTIGATION (2016)

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Article Medicine, Research & Experimental

Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies

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JOURNAL OF CLINICAL INVESTIGATION (2016)

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Review Medicine, Research & Experimental

Retroviral vectors and transposons for stable gene therapy: advances, current challenges and perspectives

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JOURNAL OF TRANSLATIONAL MEDICINE (2016)

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Article Oncology

Novel anti-CD3 chimeric antigen receptor targeting of aggressive T cell malignancies

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ONCOTARGET (2016)

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A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases

Xilin Chen et al.

ONCOTARGET (2016)

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Article Immunology

Efficient mRNA-Based Genetic Engineering of Human NK Cells with High-Affinity CD16 and CCR7 Augments Rituximab-Induced ADCC against Lymphoma and Targets NK Cell Migration toward the Lymph Node-Associated Chemokine CCL19

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FRONTIERS IN IMMUNOLOGY (2016)

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Article Oncology

Fine-tuning the CAR spacer improves T-cell potency

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ONCOIMMUNOLOGY (2016)

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Review Oncology

The role of heat shock protein 70 (Hsp70) in radiation-induced immunomodulation

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CANCER LETTERS (2015)

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Review Chemistry, Multidisciplinary

Nucleic Acid Therapeutics Using Polyplexes: A Journey of 50 Years (and Beyond)

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CHEMICAL REVIEWS (2015)

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Review Biotechnology & Applied Microbiology

Modified mRNA as an alternative to plasmid DNA (pDNA) for transcript replacement and vaccination therapy

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EXPERT OPINION ON BIOLOGICAL THERAPY (2015)

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Article Immunology

DAP12-Based Activating Chimeric Antigen Receptor for NK Cell Tumor Immunotherapy

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JOURNAL OF IMMUNOLOGY (2015)

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Article Oncology

Affinity maturation of T-cell receptor-like antibodies for Wilms tumor 1 peptide greatly enhances therapeutic potential

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LEUKEMIA (2015)

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Article Biochemistry & Molecular Biology

4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors

Adrienne H. Long et al.

NATURE MEDICINE (2015)

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Article Oncology

Selective Bispecific T Cell Recruiting Antibody and Antitumor Activity of Adoptive T Cell Transfer

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JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE (2015)

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Article Oncology

Specific growth inhibition of ErbB2-expressing human breast cancer cells by genetically modified NK-92 cells

Hui Liu et al.

ONCOLOGY REPORTS (2015)

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Article Multidisciplinary Sciences

CAR-Engineered NK Cells Targeting Wild-Type EGFR and EGFRvIII Enhance Killing of Glioblastoma and Patient-Derived Glioblastoma Stem Cells

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SCIENTIFIC REPORTS (2015)

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Article Oncology

CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma

J. Chu et al.

LEUKEMIA (2014)

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Article Oncology

A Chimeric Receptor with NKG2D Specificity Enhances Natural Killer Cell Activation and Killing of Tumor Cells

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CANCER RESEARCH (2013)

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Article Cell Biology

Retargeting NK-92 for anti-melanoma activity by a TCR-like single-domain antibody

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IMMUNOLOGY AND CELL BIOLOGY (2013)

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Article Multidisciplinary Sciences

A vector-free microfluidic platform for intracellular delivery

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

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Distinct roles of NK cells in viral immunity during different phases of acute Friend retrovirus infection

Elisabeth Littwitz et al.

RETROVIROLOGY (2013)

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Article Oncology

Expression of IL-15 in NK cells results in rapid enrichment and selective cytotoxicity of gene-modified effectors that carry a tumor-specific antigen receptor

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CANCER IMMUNOLOGY IMMUNOTHERAPY (2012)

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Article Cell & Tissue Engineering

A clinically adaptable method to enhance the cytotoxicity of natural killer cells against B-cell malignancies

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CYTOTHERAPY (2012)

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Article Biotechnology & Applied Microbiology

Inhibition of Intracellular Antiviral Defense Mechanisms Augments Lentiviral Transduction of Human Natural Killer Cells: Implications for Gene Therapy

Tolga Sutlu et al.

HUMAN GENE THERAPY (2012)

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Article Cell Biology

NK cells engineered to express a GD2-specific antigen receptor display built-in ADCC-like activity against tumour cells of neuroectodermal origin

Ruth Esser et al.

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (2012)

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Article Immunology

Dual Targeting of ErbB2 and MUC1 in Breast Cancer Using Chimeric Antigen Receptors Engineered to Provide Complementary Signaling

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Comparison of mRNA and lentiviral based transfection of natural killer cells with chimeric antigen receptors recognizing lymphoid antigens

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LEUKEMIA & LYMPHOMA (2012)

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Article Biotechnology & Applied Microbiology

Competitive electroporation formulation for cell therapy

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CANCER GENE THERAPY (2011)

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Review Biotechnology & Applied Microbiology

To Be Targeted: Is the Magic Bullet Concept a Viable Option for Synthetic Nucleic Acid Therapeutics?

Manfred Ogris et al.

HUMAN GENE THERAPY (2011)

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Article Multidisciplinary Sciences

Targeting membrane heat-shock protein 70 (Hsp70) on tumors by cmHsp70.1 antibody

Stefan Stangl et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2011)

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Review Multidisciplinary Sciences

Innate or Adaptive Immunity? The Example of Natural Killer Cells

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SCIENCE (2011)

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Article Oncology

Side-by-side analysis of five clinically tested anti-EpCAM monoclonal antibodies

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CANCER CELL INTERNATIONAL (2010)

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Article Biotechnology & Applied Microbiology

Expression of chimeric antigen receptors in natural killer cells with a regulatory-compliant non-viral method

L. Li et al.

CANCER GENE THERAPY (2010)

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Article Medicine, Research & Experimental

RD114 envelope proteins provide an effective and versatile approach to pseudotype lentiviral vectors

Anthony J. Bell et al.

EXPERIMENTAL BIOLOGY AND MEDICINE (2010)

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Article Biotechnology & Applied Microbiology

Unexpectedly High Copy Number of Random Integration but Low Frequency of Persistent Expression of the Sleeping Beauty Transposase After Trans Delivery in Primary Human T Cells

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HUMAN GENE THERAPY (2010)

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Article Oncology

2B4 (CD244) Signaling by Recombinant Antigen-specific Chimeric Receptors Costimulates Natural Killer Cell Activation to Leukemia and Neuroblastoma Cells

Bianca Altvater et al.

CLINICAL CANCER RESEARCH (2009)

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Article Medicine, Research & Experimental

Anti-tumor activity of patient-derived NK cells after cell-based immunotherapy - a case report

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JOURNAL OF TRANSLATIONAL MEDICINE (2009)

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Article Oncology

Transfection with mRNA for CD19 specific chimeric antigen receptor restores NK cell mediated killing of CLL cells

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LEUKEMIA RESEARCH (2009)

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Editorial Material Biotechnology & Applied Microbiology

Converging paths of viral and non-viral vector engineering

Ernst Wagner

MOLECULAR THERAPY (2008)

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Article Multidisciplinary Sciences

Tumor-Specific Hsp70 Plasma Membrane Localization Is Enabled by the Glycosphingolipid Gb3

Mathias Gehrmann et al.

PLOS ONE (2008)

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Article Multidisciplinary Sciences

Engineering antigen-specific primary human NK cells against HER-2 positive carcinomas

Anna Kruschinski et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

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Article Oncology

Expression of a CD20-specific chimeric antigen receptor enhances cytotoxic activity of NK cells and overcomes NK-resistance of lymphoma and leukemia cells

Tina Mueller et al.

CANCER IMMUNOLOGY IMMUNOTHERAPY (2008)

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Article Hematology

Epstein!Barr virus-specific cytotoxic T lymphocytes expressing the anti-CD30ξ artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease

Barbara Savoldo et al.

BLOOD (2007)

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Article Oncology

Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer

Maurizio Scaltriti et al.

JOURNAL OF THE NATIONAL CANCER INSTITUTE (2007)

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Article Multidisciplinary Sciences

Gene transfer in humans using a conditionally replicating lentiviral vector

Bruce L. Levine et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2006)

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Article Hematology

High-efficient lentiviral vector-mediated gene transfer into primary human NK cells

Federica Micucci et al.

EXPERIMENTAL HEMATOLOGY (2006)

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Review Oncology

Epidermal growth factor receptor targeting in cancer

John Mendelsohn et al.

SEMINARS IN ONCOLOGY (2006)

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Article Biotechnology & Applied Microbiology

Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration

Eugenio Montini et al.

NATURE BIOTECHNOLOGY (2006)

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Article Immunology

NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural killer cells

JL Upshaw et al.

NATURE IMMUNOLOGY (2006)

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Article Biochemical Research Methods

Nucleofection of non-B cells with mini-Epstein-Barr virus DNA

J Radons et al.

JOURNAL OF IMMUNOLOGICAL METHODS (2005)

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Article Hematology

Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells

C Imai et al.

BLOOD (2005)

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Review Immunology

NK cell recognition

LL Lanier

ANNUAL REVIEW OF IMMUNOLOGY (2005)

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Article Biochemical Research Methods

Cost efficient and effective gene transfer into the human natural killer cell line, NK92

EM Grund et al.

JOURNAL OF IMMUNOLOGICAL METHODS (2005)

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Article Biochemical Research Methods

Efficient infection of human natural killer cells with an EBV/retroviral hybrid vector

B Becknell et al.

JOURNAL OF IMMUNOLOGICAL METHODS (2005)

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Article Oncology

Treatment of colon and lung cancer patients with ex vivo heat shock protein 70-peptide-activated, autologous natural killer cells:: a clinical phase I trial

SW Krause et al.

CLINICAL CANCER RESEARCH (2004)

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Article Hematology

CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2:: a potential new link between adaptive and innate immunity

TA Fehniger et al.

BLOOD (2003)

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Article Biochemical Research Methods

Rapid and highly efficient gene transfer into natural killer cells by nucleofection

HI Trompeter et al.

JOURNAL OF IMMUNOLOGICAL METHODS (2003)

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Article Biochemistry & Molecular Biology

Polybrene increases retrovirus gene transfer efficiency by enhancing receptor-independent virus adsorption on target cell membranes

HE Davis et al.

BIOPHYSICAL CHEMISTRY (2002)

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Article Biotechnology & Applied Microbiology

Overcoming the nuclear barrier: Cell cycle independent nonviral gene transfer with linear polyethylenimine or electroporation

S Brunner et al.

MOLECULAR THERAPY (2002)

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Review Immunology

The biology of human natural killer-cell subsets

MA Cooper et al.

TRENDS IN IMMUNOLOGY (2001)

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Article Biochemistry & Molecular Biology

Human dendritic cells transfected with either RNA or DNA encoding influenza matrix protein M1 differ in their ability to stimulate cytotoxic T lymphocytes

I Strobel et al.

GENE THERAPY (2000)

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