美国基因泰克公司Christopher M. Rose、Benjamin Haley和Craig Blanchette团队，系统揭示了患者和肿瘤共有新抗原的新表位-人类白细胞抗原（HLA）对。2023年10月19日出版的《自然-生物技术》发表了这项成果。

为了扩大已知共享新抗原-人类白细胞抗原（HLA）复合物的范围，研究人员研发了一个高通量平台，该平台将体外多肽-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，并与包含47种常见癌症新抗原的转基因结合。从24,000多种可能的新抗原-HLA组合中，研究通过生化和计算评估得出了844个独特的候选组合，其中86个候选组合在对工程化单等位基因细胞系进行免疫沉淀质谱分析后得到了验证。

为了评估潜在的免疫原性，研究人员确定了能选择性识别特定新表位-HLA对的T细胞受体，并在导入人类T细胞后能诱导应答反应。这些细胞系统和该研究揭示的与HLA治疗相关的新表位数据将有助于研究靶向抗原处理和新表位的治疗方法。

据了解，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新表位数量的限制。

附：英文原文

Title: Systematic discovery of neoepitope–HLA pairs for neoantigens shared among patients and tumor types

Author: Gurung, Hem R., Heidersbach, Amy J., Darwish, Martine, Chan, Pamela Pui Fung, Li, Jenny, Beresini, Maureen, Zill, Oliver A., Wallace, Andrew, Tong, Ann-Jay, Hascall, Dan, Torres, Eric, Chang, Andy, Lou, Kenny Hei-Wai, Abdolazimi, Yassan, Hammer, Christian, Xavier-Magalhes, Ana, Marcu, Ana, Vaidya, Samir, Le, Daniel D., Akhmetzyanova, Ilseyar, Oh, Soyoung A., Moore, Amanda J., Uche, Uzodinma N., Laur, Melanie B., Notturno, Richard J., Ebert, Peter J. R., Blanchette, Craig, Haley, Benjamin, Rose, Christopher M.

Issue&Volume: 2023-10-19

Abstract: 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.

DOI: 10.1038/s41587-023-01945-y

Source: https://www.nature.com/articles/s41587-023-01945-y