Antibody-based immunotherapies show clinical effectiveness in various cancer types. However, the target repertoire is limited to surface or soluble antigens, which are a relatively small percentage of the cancer proteome. Most proteins of the human proteome are intracellular. Short peptides from intracellular targets can be presented by MHC class I (MHC-I) molecules on cell surface, making them potential targets for cancer immunotherapy. Antibodies can be developed to target these peptide/MHC complexes, similar to the recognition of such complexes by the T-cell receptor (TCR). These antibodies are referred to as T-cell receptor mimic (TCRm) or TCR-like antibodies. Ongoing preclinical and clinical studies will help us understand their mechanisms of action and selection of target epitopes for immunotherapy. The present review will summarize and discuss the selection of intracellular antigens, production of the peptide/MHC complexes, isolation of TCRm antibodies for therapeutic applications, limitations of TCRm antibodies, and possible ways to advance TCRm antibody-based approaches into the clinic.

中文翻译：

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用于癌症免疫治疗的 T 细胞受体模拟抗体

基于抗体的免疫疗法在各种癌症类型中显示出临床有效性。然而，目标库仅限于表面或可溶性抗原，它们在癌症蛋白质组中所占比例相对较小。人类蛋白质组的大多数蛋白质是细胞内的。来自细胞内靶标的短肽可以通过细胞表面的 MHC I 类 (MHC-I) 分子呈递，使其成为癌症免疫治疗的潜在靶标。可以开发抗体来靶向这些肽/MHC 复合物，类似于 T 细胞受体 (TCR) 对此类复合物的识别。这些抗体被称为 T 细胞受体模拟物 (TCRm) 或 TCR 样抗体。正在进行的临床前和临床研究将帮助我们了解它们的作用机制和免疫治疗靶表位的选择。