Self-Tumor Antigens in Solid Tumors Turned into Vaccines by α-gal Micelle Immunotherapy DOI Creative Commons
Uri Galili

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(10), P. 1263 - 1263

Published: Sept. 27, 2024

A major reason for the failure of immune system to detect tumor antigens (TAs) is insufficient uptake, processing, and presentation TAs by antigen-presenting cells (APCs). The immunogenicity in individual patient can be markedly increased situ targeting robust uptake APCs, without need identify characterize TAs. This feasible intra-tumoral injection α-gal micelles comprised glycolipids presenting carbohydrate-antigen "α-gal epitope" (Galα1-3Galβ1-4GlcNAc-R). Humans produce a natural antibody called "anti-Gal" (constituting ~1% immunoglobulins), which binds epitopes. Tumor-injected spontaneously insert into cell membranes, so that multiple epitopes are presented on cells. Anti-Gal binding these activates complement system, resulting killing cells, recruitment APCs (dendritic macrophages) treated tumors chemotactic cleavage peptides C5a C3a. In this process converting personalized TA vaccine, recruited APC phagocytose anti-Gal opsonized internalized transport them regional lymph-nodes. activate TA-specific T proliferate destroy metastatic Studies anti-Gal-producing mice demonstrated induction effective protection against distant metastases highly tumorigenic B16 melanoma following synthetic primary tumors. treatment was further found synergize with checkpoint inhibitor therapy anti-PD1 antibody. Phase-1 clinical trials indicated micelle immunotherapy safe induce infiltration CD4+ CD8+ untreated metastases. It suggested that, addition an autologous should considered as neoadjuvant therapy, administering immediately their detection. Such will convert anti-TA vaccine period prior resection.

Language: Английский

Neoantigens in cancer immunotherapy: focusing on alternative splicing DOI Creative Commons
Peng Huang,

Feng Wen,

Nuerye Tuerhong

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 11, 2024

Alternative splicing (AS) functions as a crucial program in transcriptional modulation, leading to proteomic diversity and functional alterations of proteins. These actions induce various neoantigens that hold prognostic significance contribute aspects cancer progression, including immune responses against cancer. The advent immunotherapy has remarkably revolutionized tumor therapy. In this regard, AS-derived are potent targets for vaccines chimeric antigen receptor (CAR) T cell therapies. review, we outline serve promising immunotherapeutic guide strategies. This evidence contributes deeper comprehension the complexity provides novel perspectives techniques precision medicine immunotherapy. Moreover, underscore obstacles awaited be addressed approach become clinically applicable.

Language: Английский

Citations

10
Evoking the Cancer-immunity cycle by targeting the tumor-specific antigens in Cancer immunotherapy DOI
Xiaomeng Guo, Junqiang Bai, Xinmiao Wang

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 154, P. 114576 - 114576

Published: April 2, 2025

Language: Английский

Citations

0
Neoantigen-based immunotherapy: advancing precision medicine in cancer and glioblastoma treatment through discovery and innovation DOI Creative Commons
Moawiah M. Naffaa, Ola A Al-Ewaidat, Sopiko Gogia

et al.

Exploration of Targeted Anti-tumor Therapy, Journal Year: 2025, Volume and Issue: 6

Published: April 27, 2025

Neoantigen-based immunotherapy has emerged as a transformative approach in cancer treatment, offering precision medicine strategies that target tumor-specific antigens derived from genetic, transcriptomic, and proteomic alterations unique to cells. These neoantigens serve highly specific targets for personalized therapies, promising more effective tailored treatments. The aim of this article is explore the advances neoantigen-based highlighting successful treatments such vaccines, tumor-infiltrating lymphocyte (TIL) therapy, T-cell receptor-engineered T cells therapy (TCR-T), chimeric antigen receptor (CAR-T), particularly types like glioblastoma (GBM). Advances technologies next-generation sequencing, RNA-based platforms, CRISPR gene editing have accelerated identification validation neoantigens, moving them closer clinical application. Despite results, challenges tumor heterogeneity, immune evasion, resistance mechanisms persist. integration AI-driven tools multi-omic data refined neoantigen discovery, while combination therapies are being developed address issues suppression scalability. Additionally, discusses ongoing development immunotherapies targeting mutations, emphasizing need continued collaboration between computational experimental approaches. Ultimately, cutting-edge research holds potential revolutionize care, hope targeted

Language: Английский

Citations

0
Neoantigen vaccines: advancing personalized cancer immunotherapy DOI Creative Commons
Alaa A. A. Aljabali,

Yassmen Hamzat,

Alaa Alqudah

et al.

Exploration of Immunology, Journal Year: 2025, Volume and Issue: 5

Published: April 8, 2025

Neoantigen vaccines are a promising strategy in cancer immunotherapy that leverage tumor-specific mutations to elicit targeted immune responses. Although they have considerable potential, development challenges related antigen prediction accuracy, manufacturing complexity, and scalability remain key obstacles their widespread clinical use. This literature review was conducted using PubMed, Scopus, Web of Science, Google Scholar databases identify relevant studies. Keywords included “neoantigen vaccines,” “personalized immunotherapy,” “tumor heterogeneity,” “bioinformatics pipelines,” “prediction algorithms”. Clinical trial data were sourced from ClinicalTrials.gov, Trialtrove, other publicly available registries. Eligible studies peer-reviewed research articles, systematic reviews, trials focusing on neoantigen vaccine development, bioinformatic strategies, immunotherapy. Tumor heterogeneity clonal evolution significantly impact efficacy, necessitating multi-epitope targeting adaptive design. Current algorithms suffer high false-positive false-negative rates, requiring further integration with multi-omics machine learning enhance accuracy. Manufacturing remains complex, time-intensive, costly, advancements standardization automation. Combination therapies, such as checkpoint inhibitors adoptive cell counteract the immunosuppressive tumor microenvironment, improving treatment outcomes. hold great potential for personalized therapy but require bioinformatics, scalability, immunomodulatory strategies efficacy. Continued interdisciplinary collaboration essential refining applications.

Language: Английский

Citations

0
Self-Tumor Antigens in Solid Tumors Turned into Vaccines by α-gal Micelle Immunotherapy DOI Creative Commons
Uri Galili

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(10), P. 1263 - 1263

Published: Sept. 27, 2024

A major reason for the failure of immune system to detect tumor antigens (TAs) is insufficient uptake, processing, and presentation TAs by antigen-presenting cells (APCs). The immunogenicity in individual patient can be markedly increased situ targeting robust uptake APCs, without need identify characterize TAs. This feasible intra-tumoral injection α-gal micelles comprised glycolipids presenting carbohydrate-antigen "α-gal epitope" (Galα1-3Galβ1-4GlcNAc-R). Humans produce a natural antibody called "anti-Gal" (constituting ~1% immunoglobulins), which binds epitopes. Tumor-injected spontaneously insert into cell membranes, so that multiple epitopes are presented on cells. Anti-Gal binding these activates complement system, resulting killing cells, recruitment APCs (dendritic macrophages) treated tumors chemotactic cleavage peptides C5a C3a. In this process converting personalized TA vaccine, recruited APC phagocytose anti-Gal opsonized internalized transport them regional lymph-nodes. activate TA-specific T proliferate destroy metastatic Studies anti-Gal-producing mice demonstrated induction effective protection against distant metastases highly tumorigenic B16 melanoma following synthetic primary tumors. treatment was further found synergize with checkpoint inhibitor therapy anti-PD1 antibody. Phase-1 clinical trials indicated micelle immunotherapy safe induce infiltration CD4+ CD8+ untreated metastases. It suggested that, addition an autologous should considered as neoadjuvant therapy, administering immediately their detection. Such will convert anti-TA vaccine period prior resection.

Language: Английский

Citations

1