HLA Fully-Mismatched Sibling-Derived CD7 CAR-T Therapy Bridging to Haploidentical Hematopoietic Stem Cell Transplantation for Hepatosplenic ?d T-cell Lymphoma

Article Oncology

Long-term follow-up of donor-derived CD7 CAR T-cell therapy in patients with T-cell acute lymphoblastic leukemia

Yue Tan et al.

Summary: In this long-term follow-up study, donor-derived CD7 CAR T-cell treatment showed durable efficacy in a subset of patients with r/r T-ALL. However, disease relapse and severe infection were major causes of treatment failure.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2023)

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Article Oncology

Single-Cell Transcriptomics Reveals Immune Reconstitution in Patients with R/R T-ALL/LBL Treated with Donor-Derived CD7 CAR-T Therapy

Wei Chen et al.

Summary: This study evaluated the safety and efficacy of donor-derived CD7 chimeric antigen receptor T (CAR-T) therapy in patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL). The results showed efficient expansion of CAR-T cells and significant increase in CD7(+) T cells. Single-cell RNA sequencing revealed stronger immunologic activities of CD7(-) T cells after CAR-T therapy, possibly due to higher expression levels of autoimmune-related pathways.

CLINICAL CANCER RESEARCH (2023)

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Article Multidisciplinary Sciences

Decade-long leukaemia remissions with persistence of CD4(+) CAR T cells

J. Joseph Melenhorst et al.

Summary: CAR T cells redirected to target CD19 demonstrated long-lasting potential and clonal stability in two patients with chronic lymphocytic leukaemia. Highly activated CD4(+) cells emerged and dominated the CAR T cell population at later time points. These unexpected CAR T cell populations provide novel insights into anti-cancer response and long-term remission in leukaemia.

NATURE (2022)

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Article Medicine, General & Internal

Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma

F. L. Locke et al.

Summary: This international phase 3 trial showed that axicabtagene ciloleucel therapy significantly improved event-free survival and response in patients with early relapsed or refractory large B-cell lymphoma compared to standard care, despite the expected high-grade toxic effects.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Article Oncology

Haploidentical CD7 CAR T-cells induced remission in a patient with TP53 mutated relapsed and refractory early T-cell precursor lymphoblastic leukemia/lymphoma

Hai-ping Dai et al.

Summary: This case demonstrates that CD7-CART is an effective and safe salvage therapy in patients with relapsed/refractory ETP-ALL/LBL and high tumor burden.

BIOMARKER RESEARCH (2022)

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Review Oncology

Chimeric Antigen Receptor Based Cellular Therapy for Treatment Of T-Cell Malignancies

Kamila Polgarova et al.

Summary: T-cell malignancies can be divided into precursor and mature types, with aggressive behavior and poor prognosis. Targeted therapies are only effective in subsets of patients. CAR-T cell therapy shows potential for T-cell malignancies, but specific obstacles need to be addressed. Further research is needed to optimize CAR-based products and evaluate long-term outcomes.

FRONTIERS IN ONCOLOGY (2022)

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Article Biotechnology & Applied Microbiology

Frequent aneuploidy in primary human T cells after CRISPR-Cas9 cleavage

Alessio David Nahmad et al.

Summary: In this study, the outcomes of genome editing in CRISPR-Cas9 transfected primary human T cells were investigated using single-cell RNA sequencing. The study revealed that chromosomal abnormalities and truncations are common outcomes of CRISPR-Cas9 cleavage, and are associated with reduced cell proliferation and cell death.

NATURE BIOTECHNOLOGY (2022)

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Article Multidisciplinary Sciences

TP53-dependent toxicity of CRISPR/Cas9 cuts is differential across genomic loci and can confound genetic screening

Miguel M. Alvarez et al.

Summary: Research indicates that TPS3-associated break toxicity is higher in genomic regions with active chromatin, while DSB repair pathway choice and DNA sequence context also play a role in toxicity. The differential toxicity of sgRNA-targeted sites can reduce the power of genetic screens to detect conditional essentiality.

NATURE COMMUNICATIONS (2022)

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Article Multidisciplinary Sciences

Endowing universal CAR T-cell with immune-evasive properties using TALEN-gene editing

Sumin Jo et al.

Summary: This study describes the development of a novel immune-evasive universal CAR T-cell scaffold, which allows CAR-T cells to evade destruction by host T and NK cells in an allogeneic setting, thereby prolonging their persistence and antitumor activity in vivo.

NATURE COMMUNICATIONS (2022)

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Article Cell Biology

Genetically modified CD7-targeting allogeneic CAR-T cell therapy with enhanced efficacy for relapsed/refractory CD7-positive hematological malignancies: a phase I clinical study

Yongxian Hu et al.

Summary: This study developed healthy donor-derived CD7-targeting allogeneic CAR-T cells with genetic modifications and conducted a phase I clinical trial. The results demonstrated the encouraging safety and efficacy profiles of the RD13-01 allogeneic CAR-T cells for CD7(+) tumors.

CELL RESEARCH (2022)

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Article Oncology

Eradication of T-ALL Cells by CD7-targeted Universal CAR-T Cells and Initial Test of Ruxolitinib-based CRS Management

Shiqi Li et al.

Summary: The study reports two cases of patients with relapsed/refractory T-ALL treated with GC027, showing robust expansion of CAR-T cells and rapid eradication of CD7(+) T lymphoblasts. Both patients achieved complete remission with no minimal residual disease. One patient remained in ongoing remission for over 1 year after CAR T-cell infusion. Grade 3 cytokine release syndrome occurred in both patients and was managed with a novel approach using ruxolitinib. No graft-versus-host disease was observed. These findings suggest that GC027 may be a promising new approach for treating refractory/relapsed T-ALL. Further studies are needed.

CLINICAL CANCER RESEARCH (2021)

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Article Genetics & Heredity

Chromothripsis as an on-target consequence of CRISPR-Cas9 genome editing

Mitchell L. Leibowitz et al.

Summary: CRISPR-Cas9 editing can result in nuclear structural defects, formation of micronuclei and chromosome bridges, leading to a mutational process known as chromothripsis. Chromothripsis, extensive chromosome rearrangement restricted to one or a few chromosomes, can cause human congenital disease and cancer. The potential for extensive chromosomal rearrangements should be considered and monitored as genome editing is implemented in the clinic.

NATURE GENETICS (2021)

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Article Oncology

Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial

Jing Pan et al.

Summary: Donor-derived anti-CD7 CAR T cells showed efficient expansion and high complete remission rate in patients with r/r T-ALL, with manageable adverse events.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Review Biotechnology & Applied Microbiology