精准癌症免疫疗法的广泛应用受到患者或肿瘤类型中常见的经过验证的新表位数量的限制。为了扩展共享新抗原-人类白细胞抗原 (HLA) 复合物的已知库，我们开发了一个高通量平台，该平台将体外肽-HLA 结合测定与表达单个 HLA 等位基因的工程细胞模型结合起来，并结合包含 47 的串联转基因。常见的癌症新抗原。从超过 24,000 个可能的新表位-HLA 组合中，生化和计算评估产生了 844 个独特的候选者，其中 86 个在对工程单等位基因细胞系进行免疫沉淀质谱分析后得到验证。为了评估免疫原性的潜力，我们鉴定了识别特定新表位-HLA 对的 T 细胞受体，并在引入人类 T 细胞后引发反应。这些细胞系统和我们在 HLA 环境中与治疗相关的新表位的数据将帮助研究人员研究抗原加工以及新表位靶向疗法。© 2023。Genentech, Inc. 和 Adaptive Biotechnologies Corp.

The broad application of precision cancer immunotherapies is limited by the number of validated neoepitopes that are common among patients or tumor types. To expand the known repertoire of shared neoantigen-human leukocyte antigen (HLA) complexes, we developed a high-throughput platform that coupled an in vitro peptide-HLA binding assay with engineered cellular models expressing individual HLA alleles in combination with a concatenated transgene harboring 47 common cancer neoantigens. From more than 24,000 possible neoepitope-HLA combinations, biochemical and computational assessment yielded 844 unique candidates, of which 86 were verified after immunoprecipitation mass spectrometry analyses of engineered, monoallelic cell lines. To evaluate the potential for immunogenicity, we identified T cell receptors that recognized select neoepitope-HLA pairs and elicited a response after introduction into human T cells. These cellular systems and our data on therapeutically relevant neoepitopes in their HLA contexts will aid researchers studying antigen processing as well as neoepitope targeting therapies.© 2023. Genentech, Inc. and Adaptive Biotechnologies Corp.