Mutation-derived neoantigens are taking central stage as a determinant in eliciting effective antitumor immune responses following adoptive T-cell therapies. These mutations are patient-specific, and their targeting calls for highly personalized pipelines. The promising clinical outcomes of tumor-infiltrating lymphocyte (TIL) therapy have spurred interest in generating T-cell infusion products that have been selectively enriched in neoantigen (or autologous tumor) reactivity. The implementation of an isolation step, prior to T-cell in vitro expansion and reinfusion, may provide a way to improve the overall response rates achieved to date by adoptive T-cell therapies in metastatic cancer patients. Here we provide an overview of the main technologies [i.e., peptide major histocompatibility complex (pMHC) multimers, cytokine capture, and activation markers] to enrich infiltrating or circulating T-cells in predefined neoantigen specificities (or tumor reactivity). The unique technical and regulatory challenges faced by such highly specialized and patient-specific manufacturing T-cell platforms are also discussed.

在过继T细胞疗法后，突变衍生的新抗原在引发有效的抗肿瘤免疫反应中起着决定性作用。这些突变是特定于患者的，其靶向性要求高度个性化的流程。肿瘤浸润淋巴细胞（TIL）治疗的有希望的临床结果激发了人们对产生T细胞输注产品的兴趣，该产品已选择性地富集了新抗原（或自体肿瘤）反应性。在T单元之前执行隔离步骤体外扩大和再输注可能会提供一种方法，以提高迄今为止通过转移性T细胞疗法对转移性癌症患者的总体缓解率。在这里，我们概述了主要技术[即，肽主要组织相容性复合物（pMHC）多聚体，细胞因子捕获和激活标记物]，可以以预定的新抗原特异性（或肿瘤反应性）富集浸润或循环的T细胞。还讨论了这种高度专业化和针对特定患者的制造T细胞平台所面临的独特技术和法规挑战。