☆ 4.8 Review

Materials engineering strategies for cancer vaccine adjuvant development

CHEMICAL SOCIETY REVIEWS (2023)

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A nanoadjuvant that dynamically coordinates innate immune stimuli activation enhances cancer immunotherapy and reduces immune cell exhaustion

Seung Mo Jin et al.

Summary: In this study, a kinetically activating nanoadjuvant (K-nanoadjuvant) is proposed to integrate two waves of innate immune stimuli, resulting in effective antitumour immunity without immune cell exhaustion. The combinatorial code of K-nanoadjuvant is optimized in terms of the order, duration, and time window between activating Toll-like receptor 7/8 agonist and other Toll-like receptor agonists. K-nanoadjuvant induces effector/non-exhausted dendritic cells, CD8(+) T cells, and natural killer cells, leading to strong antitumour immunity with minimal toxicity when used as a monotherapy or in combination therapy with other treatments.

NATURE NANOTECHNOLOGY (2023)

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Article Chemistry, Multidisciplinary

Dual-miRNA-Propelled Three-Dimensional DNA Walker for Highly Specific and Rapid Discrimination of Breast Cancer Cell Subtypes in Clinical Tissue Samples

Yanan Wu et al.

Summary: This study developed a DNA walker for rapid detection and discrimination of breast cancer cell subtypes. The method enables direct detection in clinical samples through detection of dual-miRNAs, and dramatically improves the sensitivity. It can also distinguish fluctuations in single cells.

CCS CHEMISTRY (2023)

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Article Chemistry, Multidisciplinary

A Minimalist Binary Vaccine Carrier for Personalized Postoperative Cancer Vaccine Therapy

Jiayu Zhao et al.

Summary: A minimalist binary nanovaccine (BiVax) has been designed to integrate innate stimulating activity into the carrier to elicit robust antitumor immunity, showing promising results in inducing strong immune responses against tumor cells.

ADVANCED MATERIALS (2022)

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Article Chemistry, Multidisciplinary

The Development of Chiral Nanoparticles to Target NK Cells and CD8+ T Cells for Cancer Immunotherapy

Weiwei Wang et al.

Summary: This study discovers the potential of chiral nanomaterials as immunoadjuvants for the prevention and treatment of cancer. Chiral nanoparticles enhance immune response and inhibit tumor growth through the stimulation of specific cell types, showing better therapeutic effects compared to achiral nanoparticles.

ADVANCED MATERIALS (2022)

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Article Biochemistry & Molecular Biology

Magnesium sensing via LFA-1 regulates CD8+ T cell effector function

Jonas Loetscher et al.

Summary: This study reveals the importance of extracellular magnesium in cellular immunity, particularly in the activation of the co-stimulatory molecule LFA-1. The findings demonstrate that magnesium-sufficiency enhances the function of immune cells and the effectiveness of T cell therapies. Low serum magnesium levels are associated with disease progression and reduced overall survival in patients receiving CAR T cell and immune checkpoint antibody treatments.

CELL (2022)

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Review Chemistry, Multidisciplinary

Metal-based anticancer agents as immunogenic cell death inducers: the past, present, and future

Sajal Sen et al.

Summary: Cancer is the second deadliest disease worldwide, and immunotherapy using immunogenic cell death (ICD) shows promise in overcoming treatment limitations. Metal-based complexes have been identified as potential ICD inducers. This review assesses the progress in this field and sets the stage for future advances.

CHEMICAL SOCIETY REVIEWS (2022)

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Article Multidisciplinary Sciences

Enantiomer-dependent immunological response to chiral nanoparticles

Liguang Xu et al.

Summary: The study explores the effects of chiral inorganic nanoparticles on complex biochemical networks and finds that different chiral nanoparticles have varying immune responses in vitro and in vivo. Nanoscale chirality can regulate the maturation of immune cells and left-handed nanoparticles show higher efficiency as adjuvants for vaccination.

NATURE (2022)

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Review Oncology

Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways

Lukas Kraehenbuehl et al.

Summary: The discovery and clinical implementation of immune-checkpoint inhibitors like CTLA4, PD-1, and PD-L1 have significantly improved outcomes for patients with advanced-stage cancers. However, a majority of patients do not respond to these agents, emphasizing the need for further research into alternative immunomodulatory pathways and targeting tumor metabolism to enhance treatment efficacy.

NATURE REVIEWS CLINICAL ONCOLOGY (2022)

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Review Biotechnology & Applied Microbiology

Identification of neoantigens for individualized therapeutic cancer vaccines

Franziska Lang et al.

Summary: This Review discusses the use of tumor-specific neoantigens in anticancer vaccines and introduces the mechanisms of neoantigen T cell recognition, as well as computational approaches to predict which neoantigens might confer proficient antitumor immunity in patients. Individualized treatment approaches are required to harness the full potential of the unique cancer mutations in each patient. Computational algorithms and machine-learning tools can be used to identify mutations, prioritize T cell-recognized antigens, and design personalized vaccines for each patient.

NATURE REVIEWS DRUG DISCOVERY (2022)

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Review Pharmacology & Pharmacy

Exosomes in cancer immunoediting and immunotherapy

Yarong Zhao et al.

Summary: As an important means of communication among cells, exosomes are increasingly studied, especially in the context of cancer immunotherapy. Exosomes derived from tumor cells and different immune cells have complex and changeable physiological functions due to carrying different proteins and nucleic acids from the source cells. Based on the role of exosomes in intercellular communication, cancer treatment methods are continuously being researched. This review briefly introduces the molecular composition of exosomes and its secretion mechanism, summarizes the role of exosomes encapsulating different information molecules, and provides a detailed introduction to the role of exosomes in the three phases of tumor immunoediting and the relevant literature of exosomes in the tumor immune microenvironment.

ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES (2022)

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Review Chemistry, Inorganic & Nuclear

Metal-based nano-vaccines for cancer immunotherapy

Jiexin Li et al.

Summary: Metalloimmunology has the potential to revitalize cancer vaccines by utilizing metal-based nanomaterials as adjuvants or delivery carriers to enhance immunity and improve the induction of antigen specific T cells for cancer immunotherapy.

COORDINATION CHEMISTRY REVIEWS (2022)

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Article Chemistry, Multidisciplinary

Maximizing TLR9 Activation in Cancer Immunotherapy with Dual-Adjuvanted Spherical Nucleic Acids br

Peiru Chen et al.

Summary: This study demonstrates that a carrier-free spherical nucleic acid-based self-adjuvanting system can serve as a potent anticancer vaccine by enhancing adaptive immunity and significantly inhibiting tumor growth and metastasis.

NANO LETTERS (2022)

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Article Chemistry, Physical

STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity

Eric L. Dane et al.

Summary: Lipid nanodiscs functionalized with STING-activating cyclic dinucleotides demonstrate superior tumour penetration and tumour cell uptake, leading to enhanced antitumour T-cell priming and tumour regression.

NATURE MATERIALS (2022)

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Article Nanoscience & Nanotechnology

Cancer immunotherapy based on image-guided STING activation by nucleotide nanocomplex-decorated ultrasound microbubbles

Xuefeng Li et al.

Summary: Researchers have developed a novel ultrasound-guided cancer immunotherapy platform that activates the immune response and enhances cancer treatment by targeting the STING pathway in APCs. This study provides a new strategy for targeted immunotherapy.

NATURE NANOTECHNOLOGY (2022)

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Article Nanoscience & Nanotechnology

A nanovaccine for antigen self-presentation and immunosuppression reversal as a personalized cancer immunotherapy strategy

Chao Liu et al.

Summary: This study presents a genetically engineered cell membrane nanovesicle for cancer immunotherapy. The nanovaccine, named ASPIRE, can improve antigen delivery to lymphoid organs and generate broad-spectrum T-cell responses that eliminate established tumors. This work provides a powerful vaccine formula that can directly activate both native T cells and exhausted T cells, suggesting a general strategy for personalized cancer immunotherapy.

NATURE NANOTECHNOLOGY (2022)

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Article Multidisciplinary Sciences

Spherical nucleic acids as an infectious disease vaccine platform

Michelle H. Teplensky et al.

Summary: This study explores how the presentation of vaccine components in spherical nucleic acids (SNAs) can induce and maximize antiviral response. The SNA vaccine, encapsulating the receptor-binding domain (RBD) subunit and decorated with Toll-like receptor 9 agonist oligonucleotides, shows promising results in inducing immune responses in human cells and mice, outperforming traditional vaccines.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

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Review Biochemistry & Molecular Biology

The landscape of mRNA nanomedicine

Xiangang Huang et al.

Summary: mRNA is an emerging therapeutic agent with great potential for revolutionizing life science and medical research. Recent progress in mRNA engineering and delivery has addressed the challenges related to stability, immunogenicity, and in vivo delivery. The success of mRNA vaccines against COVID-19 has transformed the field and opened up possibilities for treating other diseases.

NATURE MEDICINE (2022)

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Article Oncology

Cancer treatment and survivorship statistics, 2022

Kimberly D. Miller et al.

Summary: The number of cancer survivors in the United States is increasing due to population growth, aging, and improved detection and treatment. The most prevalent cancers are prostate, skin melanoma, and colon and rectum for males, and breast, uterine corpus, and thyroid for females. Treatment disparities exist, with Black patients being less likely to be diagnosed with early-stage cancer and having lower surgical receipt rates.

CA-A CANCER JOURNAL FOR CLINICIANS (2022)

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Review Oncology

Nanomedicine Penetration to Tumor: Challenges, and Advanced Strategies to Tackle This Issue

Muhammad Usman Munir

Summary: This article reviews the application of nanomedicine in tumor treatment and discusses the obstacles in tumor penetration. Although there are some methods to improve the penetration of nanomedicine, there are still problems to be solved, such as the complex tumor microenvironment and delivery issues.

CANCERS (2022)

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Article Chemistry, Multidisciplinary

Lanthanide-Nucleotide Coordination Nanoparticles for STING Activation

Zichao Luo et al.

Summary: This study presents the design and synthesis of nanoparticle formulations that can stimulate immune responses and inhibit tumor growth. These nanoparticles, which act as surrogates for STING agonists, show improved bioactivity and immune enhancement compared to traditional agonists.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2022)

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Article Nanoscience & Nanotechnology

Zinc cyclic di-AMP nanoparticles target and suppress tumours via endothelial STING activation and tumour-associated macrophage reinvigoration

Kaiting Yang et al.

Summary: Researchers have developed a metal-based polymeric nanoparticle that delivers STING agonists to tumors, disrupting endothelial cells in the tumor vasculature and targeting tumor-associated macrophages to elicit an anti-tumor immune response in hard-to-treat cancer models.

NATURE NANOTECHNOLOGY (2022)

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Article Chemistry, Multidisciplinary

Self-assembling small-molecule adjuvants as antigen nano-carriers

Shuyu Jin et al.

Summary: The effective co-delivery of antigens and immune potentiators, as well as high antigen presentation, are two major challenges in subunit vaccine development. In this study, peptide antigens were conjugated with cholicamide, a self-assembling small molecule adjuvant, to address these issues. Co-assemblies of the conjugates and cholicamide achieved high levels of both cytokine induction and MHC class II peptide presentation.

CHEMICAL COMMUNICATIONS (2022)

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Article Chemistry, Multidisciplinary

Discovery of Self-Assembling Small Molecules as Vaccine Adjuvants

Shuyu Jin et al.

Summary: A novel vaccine adjuvant utilizing a self-assembling small-molecule library was developed in this study, which strongly induced innate immune responses in macrophages and dendritic cells through activation of Toll-like receptor 7. Functional analyses showed that the adjuvant was as potent as the clinically used adjuvant Alum in mice as an influenza vaccine.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2021)

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Article Chemistry, Physical

A DNA nanodevice-based vaccine for cancer immunotherapy

Shaoli Liu et al.

Summary: A DNA nanodevice vaccine has been developed to stimulate a tumor-specific cytotoxic T lymphocyte response, leading to inhibition of tumor growth and prevention of metastasis. The vaccine utilizes molecular adjuvants and antigen peptides within a tubular DNA nanostructure to trigger T-cell activation and cancer cytotoxicity, showing promising results in mouse cancer models. The vaccination generates long-term T-cell responses which effectively protect against tumor rechallenge.

NATURE MATERIALS (2021)

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Review Pharmacology & Pharmacy

Enhancing therapeutic performance of personalized cancer vaccine via delivery vectors

Tong Ye et al.

Summary: Personalized cancer vaccines have gained attention for their ability to overcome interindividual differences and show benefits for individual patients in the clinic. Various delivery vectors, including artificial materials, engineered microorganisms, cells and cell derivatives, have been studied to enhance the therapeutic performance of personalized cancer vaccines. These delivery vectors are utilized to improve antigen distribution and immune response strength, velocity, and duration through different delivery strategies.

ADVANCED DRUG DELIVERY REVIEWS (2021)

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Review Pharmacology & Pharmacy

Delivery of STING agonists for adjuvanting subunit vaccines

Simon Van Herck et al.

Summary: This review discusses the mechanisms of STING agonists in vaccination, recent progress in novel STING agonist discovery and delivery strategies, as well as efforts in optimizing the efficacy and minimizing toxicity of STING agonist-assisted subunit vaccines. The future development of STING agonists for adjuvanting subunit vaccines is also discussed.

ADVANCED DRUG DELIVERY REVIEWS (2021)

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Review Oncology

Advances in the development of personalized neoantigen-based therapeutic cancer vaccines

Eryn Blass et al.

Summary: Immunotherapy has revolutionized cancer treatment with the development of immune-checkpoint inhibitors and personalized neoantigen vaccines. These vaccines trigger specific T cell responses against individual patient's tumors, showing promising tumor-specific immunogenicity and antitumor activity.

NATURE REVIEWS CLINICAL ONCOLOGY (2021)

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Review Chemistry, Multidisciplinary

Natural and synthetic carbohydrate-based vaccine adjuvants and their mechanisms of action

Carlo Pifferi et al.

Summary: Modern subunit vaccines based on homogeneous antigens offer precise targeting and safety, but are less immunogenic and require adjuvants. Both natural and synthetic carbohydrate structures have been used as adjuvants in clinical trials, but naturally derived ones are difficult to obtain and unstable.

NATURE REVIEWS CHEMISTRY (2021)

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Article Nanoscience & Nanotechnology

Amplifying STING activation by cyclic dinucleotide-manganese particles for local and systemic cancer metalloimmunotherapy

Xiaoqi Sun et al.

Summary: Metalloimmunotherapy utilizes metal ions to amplify the anti-tumour immune response promoted by STING agonists, forming nanoparticles that effectively deliver STING agonists and achieve remarkable therapeutic efficacy in multiple tumour models. This work highlights the great potential of coordination nanomedicine for metalloimmunotherapy.

NATURE NANOTECHNOLOGY (2021)

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Article Chemistry, Multidisciplinary

Polymeric delivery systems for nucleic acid therapeutics: Approaching the clinic

Annette I. S. van den Berg et al.

Summary: This review discusses the clinical applications of gene therapy using nucleic acids and the development of carrier systems, highlighting the drawbacks of viral vectors and the potential of non-viral carrier systems. It focuses on polymer-based nucleic acid formulations, known as polyplexes, summarizing different polymeric systems and addressing cellular barriers encountered by polyplexes. Attention is given to the clinical status of non-viral nucleic acid formulations.

JOURNAL OF CONTROLLED RELEASE (2021)

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Article Multidisciplinary Sciences

Delivery of mRNA vaccine with a lipid-like material potentiates antitumor efficacy through Toll-like receptor 4 signaling

Hongxia Zhang et al.

Summary: The C1 lipid nanoparticle-based mRNA cancer nanovaccine efficiently delivers mRNA to antigen presenting cells, activates TLR4, induces inflammatory cytokines in dendritic cells, and shows significant antitumor efficacy.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Cell Biology

A first-in-human phase 0 clinical study of RNA interference-based spherical nucleic acids in patients with recurrent glioblastoma

Priya Kumthekar et al.

Summary: The research team has developed a novel treatment approach for GBM using SNAs for precision medicine treatment, which has shown potential in clinical trials.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Article Engineering, Biomedical

Prolonged activation of innate immune pathways by a polyvalent STING agonist

Suxin Li et al.

Summary: A novel polyvalent STING agonist extends the activation of innate-immunity pathways through the formation of STING condensates and leads to synergistic therapeutic outcomes in vivo when combined with the STING ligand cGAMP.

NATURE BIOMEDICAL ENGINEERING (2021)

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Review Medicine, General & Internal

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Nicola Dalbeth et al.

Summary: Gout is a common and treatable disease caused by the deposition of monosodium urate crystals in the body, leading to arthritis. Long-term urate lowering therapy is effective in preventing gout flares and improving quality of life.

LANCET (2021)

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Review Biotechnology & Applied Microbiology

Emerging concepts in the science of vaccine adjuvants

Bali Pulendran et al.

Summary: Adjuvants are vaccine components that enhance the immune response. Recent advances in understanding the molecular mechanisms and systems vaccinology have revitalized the science and development of novel adjuvants for use in vaccines against COVID-19 and future pandemics.

NATURE REVIEWS DRUG DISCOVERY (2021)

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Review Pharmacology & Pharmacy

Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants

Sachin Bhagchandani et al.

Summary: Imidazoquinoline derivatives function as synthetic agonists of Toll-like receptors 7 and 8, with potential therapeutic utility in antitumor immunomodulation and vaccine adjuvants. However, challenges such as broad expression profiles, poor pharmacokinetic properties, and associated toxicities hinder their successful clinical translation. Strategies to enhance safety and efficacy through bioconjugates and nanoparticle formulations are being explored to address these barriers.

ADVANCED DRUG DELIVERY REVIEWS (2021)

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Article Chemistry, Multidisciplinary

Exquisite Vesicular Nanomedicine by Paclitaxel Mediated Co-assembly with Camptothecin Prodrug

Zijian Zhou et al.

Summary: By modulating the self-assembly of drug amphiphiles EB-CPT with the anticancer drug PTX, ultrahigh quality nanovesicles (NVs) were produced with high drug loading efficiency and content. The ECX NVs with EB-CPT:PTX weight ratio of 1:2 exhibited remarkable anticancer activity against cancer cells and improved tumor inhibition effect in vivo.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2021)

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Review Immunology

Molecular mechanisms of nonself nucleic acid recognition by the innate immune system

Carina C. de Oliveira Mann et al.

Summary: The innate immune system recognizes nucleic acids through a complex mechanism, distinguishing between self and nonself by positioning NA-sensing receptors in specific subcellular compartments, employing counterregulatory measures against endogenous NAs, and identifying specific nonself patterns. Recent advances in molecular mechanisms of NA recognition by TLRs, RLRs, and the cGAS-STING axis highlight differences in NA-PRR interfaces that confer specificity and selectivity towards NA ligands, along with NA-dependent induced conformational changes necessary for signal transduction.

EUROPEAN JOURNAL OF IMMUNOLOGY (2021)

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Pooyan Makvandi et al.

Materials Today (2021)

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Lymph-Node-Targeted Cholesterolized TLR7 Agonist Liposomes Provoke a Safe and Durable Antitumor Response

Dandan Wan et al.

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NANO LETTERS (2021)

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Bacterial cytoplasmic membranes synergistically enhance the antitumor activity of autologous cancer vaccines

Long Chen et al.

Summary: Utilizing Escherichia coli cytoplasmic membranes as adjuvants, a vaccine based on hybrid membrane nanoparticles containing tumor cell membranes induced sufficient antitumor reactivity without notable adverse effects, showing efficacy in various tumor mouse models and providing long-term protection against tumor rechallenge.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Review Immunology

Polyvalent design in the cGAS-STING pathway

Zachary T. Bennett et al.

Summary: Polyvalent interactions play a crucial role in forming higher-order macromolecular assemblies to enhance the sensitivity, specificity, and temporal response of biological signals. Natural and synthetic agonists in the STING signaling pathway showcase the engineering design based on polyvalency principles for effective innate immune activation.

SEMINARS IN IMMUNOLOGY (2021)

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Review Oncology

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Mansi Saxena et al.

Summary: Therapeutic cancer vaccines aim to induce tumor regression, eradicate minimal residual disease, establish lasting anti-tumor memory, and avoid non-specific or adverse reactions. However, challenges arise due to tumor-induced immunosuppression and immunoresistance, hindering the achievement of these goals.

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Peptide-TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens

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Injectable Hydrogels for Sustained Codelivery of Subunit Vaccines Enhance Humoral Immunity

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Delivery of mRNA vaccines with heterocyclic lipids increases anti-tumor efficacy by STING-mediated immune cell activation

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