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Repurposing TRM for tumor immunotherapy

重新利用 TRM 进行肿瘤免疫治疗

基本信息

批准号：
10524249
负责人：
DAVID MASOPUST
金额：
$ 0.52万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-12-04 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10524249
关键词：
Abscopal effect Adaptive Immune System Address Adjuvant Anatomy Antibodies Antigen Presentation Cancer Model Cell physiology Cells Clinical Clinical Treatment Clinical Trials Common Neoplasm Data Distant Environment Evaluation Future Goals Human Immune Immunity Immunotherapeutic agent Immunotherapy Investigation Malignant Neoplasms Measurable Modeling Mus Natural Killer Cells Patients Peptides Phenotype Preparation Primary Neoplasm Recrudescences Recurrence Role Site Solid Neoplasm Surveys T cell response T memory cell T-Lymphocyte Testing Tissues Tumor Biology Viral Virus Virus Diseases anti-PD-L1 anti-cancer antiviral immunity arm cancer immunotherapy cytokine experience fighting immune checkpoint blockade immunogenic in vivo melanoma neoantigens neoplasm immunotherapy novel strategies prevent programmed cell death ligand 1 recruit response sound synergism tumor tumor growth tumor microenvironment tumor-immune system interactions

项目摘要

Abstract: Repurposing TRM for tumor immunotherapy Overcoming the immunosuppressive tumor microenvironment and localizing adoptive cell and checkpoint blockade therapies to solid tumors remain major impediments to successful cancer immunotherapy. This proposal addresses these issues. Preliminary data indicates that human tumors are populated with antiviral T cells that remain competent to trigger immunostimulatory sensing and alarm function upon local recognition of cognate peptide. In mice, peptide alarm therapy synergizes with PD-L1 to clear tumors and mice are durably protected against tumor growth at alternative anatomic sites in the absence of further treatment. This proposal will dissect the mechanisms by which peptide alarm therapy triggers tumor clearance and establishes systemic tumor-specific immunity. It will test synergy with other immunotherapies. Further investigations will be made on the ability to recapitulate peptide alarm therapy on human tumor explants in anticipation of informing a clinical trial. This proposal may have a sustained impact on the field by defining a new avenue of cancer immunotherapy that operates independently but synergizes with other therapies.

翻译后摘要：重新利用TRM肿瘤免疫治疗克服免疫抑制肿瘤微环境并定位过继细胞和检查点对实体瘤的阻断疗法仍然是成功的癌症免疫疗法的主要障碍。这提案针对这些问题。初步数据表明，人类肿瘤中存在抗病毒T细胞，细胞在局部识别免疫刺激后仍然有能力触发免疫刺激感测和警报功能，同源肽。在小鼠中，肽警报疗法与PD-L1协同清除肿瘤，在没有进一步治疗的情况下，在替代的解剖部位防止肿瘤生长。这项建议将剖析肽报警治疗触发肿瘤清除的机制，并建立系统的肿瘤特异性免疫它将测试与其他免疫疗法的协同作用。警方将进一步调查在人肿瘤外植体上重现肽报警治疗的能力，预期告知临床审判这一提议可能会对该领域产生持续的影响，因为它定义了癌症免疫治疗的新途径。它独立运作，但与其他疗法协同作用。