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The Ways of Isolating Neoantigen-Specific T Cells.

ABSTRACT: Immunotherapy has revolutionized the standard of care for a range of malignancies. Accumulating evidence suggests that the success of immunotherapy is likely attributable to neoantigen-specific T cells. Thus, adoptive cell therapy with these neoantigen-specific T cells is highly promising. This strategy has proven to successfully elicit tumor regression or even complete remission in metastatic cancer patients. However, a fundamental challenge is to effectively identify and isolate neoantigen-specific T cells or their T cell receptors (TCRs), from either tumor-infiltrating lymphocytes (TILs) or peripheral blood lymphocytes (PBLs), and many methods have been developed to this end. In this review, we focus on the current proposed strategies for identifying and isolating neoantigen-specific T cells.

SUBMITTER: Li Q

PROVIDER: S-EPMC7431921 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Ways of Isolating Neoantigen-Specific T Cells.

Li Qing Q Ding Zhen-Yu ZY

Frontiers in oncology 20200811

Immunotherapy has revolutionized the standard of care for a range of malignancies. Accumulating evidence suggests that the success of immunotherapy is likely attributable to neoantigen-specific T cells. Thus, adoptive cell therapy with these neoantigen-specific T cells is highly promising. This strategy has proven to successfully elicit tumor regression or even complete remission in metastatic cancer patients. However, a fundamental challenge is to effectively identify and isolate neoantigen-spe ...[more]

PMID: 32850430

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Project description:BackgroundPreclinical studies and early clinical trials have shown that targeting cancer neoantigens is a promising approach towards the development of personalized cancer immunotherapies. DNA vaccines can be rapidly and efficiently manufactured and can integrate multiple neoantigens simultaneously. We therefore sought to optimize the design of polyepitope DNA vaccines and test optimized polyepitope neoantigen DNA vaccines in preclinical models and in clinical translation.MethodsWe developed and optimized a DNA vaccine platform to target multiple neoantigens. The polyepitope DNA vaccine platform was first optimized using model antigens in vitro and in vivo. We then identified neoantigens in preclinical breast cancer models through genome sequencing and in silico neoantigen prediction pipelines. Optimized polyepitope neoantigen DNA vaccines specific for the murine breast tumor E0771 and 4T1 were designed and their immunogenicity was tested in vivo. We also tested an optimized polyepitope neoantigen DNA vaccine in a patient with metastatic pancreatic neuroendocrine tumor.ResultsOur data support an optimized polyepitope neoantigen DNA vaccine design encoding long (≥20-mer) epitopes with a mutant form of ubiquitin (Ubmut) fused to the N-terminus for antigen processing and presentation. Optimized polyepitope neoantigen DNA vaccines were immunogenic and generated robust neoantigen-specific immune responses in mice. The magnitude of immune responses generated by optimized polyepitope neoantigen DNA vaccines was similar to that of synthetic long peptide vaccines specific for the same neoantigens. When combined with immune checkpoint blockade therapy, optimized polyepitope neoantigen DNA vaccines were capable of inducing antitumor immunity in preclinical models. Immune monitoring data suggest that optimized polyepitope neoantigen DNA vaccines are capable of inducing neoantigen-specific T cell responses in a patient with metastatic pancreatic neuroendocrine tumor.ConclusionsWe have developed and optimized a novel polyepitope neoantigen DNA vaccine platform that can target multiple neoantigens and induce antitumor immune responses in preclinical models and neoantigen-specific responses in clinical translation.

Dataset Information

The Ways of Isolating Neoantigen-Specific T Cells.

Publications

The Ways of Isolating Neoantigen-Specific T Cells.

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