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Neoantigens and their potential applications in tumor immunotherapy.

ABSTRACT: The incidence of malignant tumors is increasing, the majority of which are associated with high morbidity and mortality rates worldwide. The traditional treatment method for malignant tumors is surgery, coupled with radiotherapy or chemotherapy. However, these therapeutic strategies are frequently accompanied with adverse side effects. Over recent decades, tumor immunotherapy shown promise in demonstrating notable efficacy for the treatment of cancer. With the development of sequencing technology and bioinformatics algorithms, neoantigens have become compelling targets for cancer immunotherapy due to high levels of immunogenicity. In addition, neoantigen-based vaccines have demonstrated potential for cancer therapy, primarily by augmenting T-cell responses. Neoantigens have also been shown to be effective in immune checkpoint blockade therapy. Therefore, neoantigens may serve to be predictive biomarkers and synergistic treatment targets in cancer immunotherapy. The aim of the present review was to provide an overview of the recent progress in the classification, screening and clinical application of neoantigens for cancer therapy.

SUBMITTER: Fang X

PROVIDER: S-EPMC8805178 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Neoantigens and their potential applications in tumor immunotherapy.

Fang Xianzhu X Guo Zhiliang Z Liang Jinqing J Wen Jiao J Liu Yuanyuan Y Guan Xiumei X Li Hong H

Oncology letters 20220121 3

The incidence of malignant tumors is increasing, the majority of which are associated with high morbidity and mortality rates worldwide. The traditional treatment method for malignant tumors is surgery, coupled with radiotherapy or chemotherapy. However, these therapeutic strategies are frequently accompanied with adverse side effects. Over recent decades, tumor immunotherapy shown promise in demonstrating notable efficacy for the treatment of cancer. With the development of sequencing technolog ...[more]

PMID: 35126730

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Project description:BackgroundEnhancing antigen cross-presentation is essential for the development of a tumor neoantigen vaccine. One approach is to stimulate antigen-presenting cells (APCs) to uptake neoantigens. Mycobacterium tuberculosis (MTb) contains pathogen-associated molecular patterns (PAMPs) recognized by APCs and adhesion molecules that facilitate MTb invasion of APCs. Therefore, we suggest using MTb as a carrier to enhance APC phagocytosis of neoantigens, thereby promoting antigen cross-presentation.MethodsThe successful preparation of the MTb carrier (phMTb) was confirmed through electron and confocal microscopy. Fluorescence microscopy was used to detect PAMPs and adhesion molecules on phMTb as well as to observe its role in aiding dendritic cells (DCs) in antigen uptake into endosomes or lysosomes. Flow cytometry was used to assess the retention of PAMPs and adhesion molecules on phMTb, investigate antigen uptake by DCs, evaluate their activation and maturation status, examine the presentation of tumor neoantigens, and analyze immune cells in draining lymph nodes and tumor tissues. The efficacy of phMTb vaccine formulations in combination with anti-programmed cell death protein 1 (PD-1) antibody therapy was assessed using the MC38 mouse tumor models. Adverse effects were evaluated through H&E staining of major organs, assessment of reproductive capability and detection of biochemical indices.ResultsThe engineered porous hollow phMTb carrier successfully encapsulated model tumor neoantigens, with or without the adjuvant CpG. The phMTb retained PAMPs and adhesion molecules on its surface, similar to the parental MTb, thereby enhancing DC uptake of phMTb and its formulations containing tumor neoantigens and CpG. Vaccines formulated with phMTb facilitated DC maturation, activation, cross-presentation of tumor neoantigens, and promoted migration of phMTb-laden DCs to lymph nodes, enhancing effector and memory CD8+ T lymphocyte function. In murine tumor models, immunization with phMTb-formulated neoantigen vaccines elicited a robust tumor-specific cytotoxic T lymphocyte immune response with minimal adverse effects. Additionally, vaccination with phMTb-formulated neoantigen vaccines effectively reversed the tumor's immune-suppressive microenvironment. Concurrent administration of the PD-1 antibody with the phMTb-formulated neoantigen vaccine exhibited significant synergistic therapeutic effects.ConclusionsThe results of our study highlight the potential clinical translation of personalized tumor neoantigen vaccines using the phMTb carrier.

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Neoantigens and their potential applications in tumor immunotherapy.

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Neoantigens and their potential applications in tumor immunotherapy.

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