Intratumoral immune triads are required for immunotherapy-mediated elimination of solid tumors

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(7), P. 1202 - 1216.e8

Published: June 20, 2024

Language: Английский

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DNA Vaccines: Their Formulations, Engineering and Delivery

Vaccines, Journal Year: 2024, Volume and Issue: 12(1), P. 71 - 71

Published: Jan. 11, 2024

The concept of DNA vaccination was introduced in the early 1990s. Since then, advancements augmentation immunogenicity vaccines have brought this technology to market, especially veterinary medicine, prevent many diseases. Along with successful COVID mRNA vaccines, first vaccine for human use, Indian ZyCovD against SARS-CoV-2, approved 2021. In current review, we give an overview focusing on science, including adjuvants and delivery methods. We then cover some emerging science field notably efforts optimize systems, better engineer apparatuses, identify optimal sites, personalize cancer immunotherapy through vaccination, enhance adjuvant gene adjuvants, off-target heritable immunity epigenetic modification, predict epitopes bioinformatic approaches. also discuss major limitations aim address theoretical concerns.

Language: Английский

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Neoantigen-specific cytotoxic Tr1 CD4 T cells suppress cancer immunotherapy

Nature, Journal Year: 2024, Volume and Issue: 632(8023), P. 182 - 191

Published: July 24, 2024

Abstract CD4 + T cells can either enhance or inhibit tumour immunity. Although regulatory have long been known to impede antitumour responses 1–5 , other recently implicated in inhibiting this response 6,7 . Yet, the nature and function of latter remain unclear. Here, using vaccines containing MHC class I (MHC-I) neoantigens (neoAgs) different doses tumour-derived MHC-II neoAgs, we discovered that whereas inclusion with low MHC-II-restricted peptides (LDVax) promoted rejection, high same neoAgs (HDVax) inhibited rejection. Characterization inhibitory induced by HDVax identified them as type 1 (Tr1) expressing IL-10, granzyme B, perforin, CCL5 LILRB4. Tumour-specific Tr1 suppressed rejection anti-PD1, LDVax adoptively transferred tumour-specific effector cells. Mechanistically, HDVax-induced selectively killed antigen-presenting conventional dendritic (cDC1s), leading numbers cDC1s tumours. We then documented modalities overcome inhibition, specifically via anti-LILRB4 blockade, a CD8-directed IL-2 mutein, targeted loss cDC2/monocytes. Collectively, these data show cytotoxic cells, which maintain peripheral tolerance, also thereby immune control cancer.

Language: Английский

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Neoantigen-specific stem cell memory-like CD4+ T cells mediate CD8+ T cell-dependent immunotherapy of MHC class II-negative solid tumors

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(8), P. 1345 - 1357

Published: July 3, 2023

CD4

Language: Английский

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Advancing nanotechnology for neoantigen-based cancer theranostics

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(7), P. 3224 - 3252

Published: Jan. 1, 2024

Neoantigens play a pivotal role in the field of tumour therapy, encompassing stimulation anti-tumour immune response and enhancement targeting capability. Nonetheless, numerous factors directly influence effectiveness neoantigens bolstering responses, including neoantigen quantity specificity, uptake rates by antigen-presenting cells (APCs), residence duration within microenvironment (TME), their ability to facilitate maturation APCs for activation. Nanotechnology assumes significant several aspects, facilitating release, promoting delivery cells, augmenting dendritic shielding from protease degradation, optimizing interactions between system. Consequently, development nanotechnology synergistically enhances efficacy cancer theranostics. In this review, we provide an overview sources, mechanisms neoantigen-induced evolution precision neoantigen-based nanomedicine. This encompasses various therapeutic modalities, such as immunotherapy, phototherapy, radiotherapy, chemotherapy, chemodynamic other strategies tailored augment therapeutics. We also discuss current challenges prospects application nanomedicine, aiming expedite its clinical translation.

Language: Английский

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Cancer neoepitopes viewed through negative selection and peripheral tolerance: a new path to cancer vaccines

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(5)

Published: Feb. 29, 2024

A proportion of somatic mutations in tumors create neoepitopes that can prime T cell responses target the MHC I-neoepitope complexes on tumor cells, mediating control or rejection. Despite compelling centrality to cancer immunity, we know remarkably little about what constitutes a neoepitope mediate vivo and distinguishes such from vast majority similar candidate are inefficacious vivo. Studies mice as well clinical trials have begun reveal unexpected paradoxes this area. Because straddle ambiguous ground between self non-self, some rules fundamental immunology frankly non-self antigens, viral model do not appear apply neoepitopes. so self-epitopes, with only small changes render them immune response is regulated at least partially way regulated. Therefore, viewed understood here through clarifying lens negative thymic selection. Here, emergent questions biology applications discussed critically mechanistic testable framework explains complexity translational potential these wonderful antigens proposed.

Language: Английский

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In vivo armed macrophages curb liver metastasis through tumor-reactive T-cell rejuvenation

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 11, 2025

Despite recent progress in cancer treatment, liver metastases persist as an unmet clinical need. Here, we show that arming and tumor-associated macrophages vivo to co-express tumor antigens (TAs), IFNα, IL-12 unleashes robust anti-tumor immune responses, leading the regression of metastases. Mechanistically, armed expand reactive CD8+ T cells, which acquire features progenitor exhausted cells kill independently CD4+ cell help. IFNα produced by reprogram antigen presenting rewire cellular interactions, rescuing functions. In trigger immunity distinct metastasis mouse models colorectal melanoma, expressing either surrogate antigens, naturally occurring neoantigens or antigens. Altogether, our findings support translational potential rejuvenate for treatment

Language: Английский

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Advancements in adoptive CAR immune cell immunotherapy synergistically combined with multimodal approaches for tumor treatment

Bioactive Materials, Journal Year: 2024, Volume and Issue: 42, P. 379 - 403

Published: Sept. 10, 2024

Language: Английский

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A functional identification platform reveals frequent, spontaneous neoantigen-specific T cell responses in patients with cancer

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(736)

Published: Feb. 28, 2024

The clinical impact of tumor-specific neoantigens as both immunotherapeutic targets and biomarkers has been impeded by the lack efficient methods for their identification validation from routine samples. We have developed a platform that combines bioinformatic analysis tumor exomes transcriptional data with functional testing autologous peripheral blood mononuclear cells (PBMCs) to simultaneously identify validate recognized naturally primed CD4 + CD8 T cell responses across range types mutational burdens. method features human leukocyte antigen (HLA)–agnostic algorithm prioritizes mutations patient PBMCs at greater than 40% positive predictive value followed short-term in vitro assay, which allows interrogation 50 75 expressed single 50-ml sample. Neoantigens validated this include driver passenger mutations, identified would not otherwise detected using an silico prediction approach. These findings reveal approach systematically clinically actionable receptors recognize them demonstrate patients variety cancers diverse repertoire neoantigen-specific cells.

Language: Английский

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Mannan-Decorated Lipid Calcium Phosphate Nanoparticle Vaccine Increased the Antitumor Immune Response by Modulating the Tumor Microenvironment

Journal of Functional Biomaterials, Journal Year: 2024, Volume and Issue: 15(8), P. 229 - 229

Published: Aug. 16, 2024

With the rapid development of tumor immunotherapy, nanoparticle vaccines have attracted much attention as potential therapeutic strategies. A systematic review and analysis must be carried out to investigate effect mannose modification on immune response nanoparticles in regulating microenvironment, well explore its clinical application therapy. Despite advantages achieving an effective microenvironment remains a challenge. Tumor escape overexpression immunosuppressive factors limit application. Therefore, our explored how intervene mechanism through use mannan-decorated lipid calcium phosphate improve efficacy immunotherapy patients with tumors provide new ideas strategies for field

Language: Английский

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