Zhao Qi
Institute of Translational Medicine, Cancer Centre, Biological Imaging & Stem Cell Core, Faculty of Health Sciences, University of Macau, Taipa, Macau SPR, China.
Blood Sci. 2019 Oct 21;1(2):144-147. doi: 10.1097/BS9.0000000000000032. eCollection 2019 Oct.
The need for novel therapeutics against human cancers such as leukemias and solid tumors is well recognized. Human T cells are poised to make a fundamental change in the therapeutic approach. T-cell interaction with a tumor cell is a critical event and primarily driven by T-cell receptor (TCR) recognition of peptide in the pocket HLA. However, among TCR-based T-cell therapies, either TCR mismatching or the low density of major histocompatibility complex causes tumor cells to escape from the immune response. TCR molecules have low binding affinities, preventing their recognitions. Undoubtedly, antibody therapeutics is an effective treatment for cancer. As the new generation of monoclonal antibodies, TCR-like antibodies can mimic TCR recognition but are not susceptible for mechanisms of tumor evasion from the immune response. As chimeric antigen receptor (CAR) structure expressed on the surface of T cells, TCR-like antibodies can confer antigen specificity to T cells. The new TCR-like CAR may be important to drive new technologies of adoptive cell therapy, in particular, T-cell therapy, and open possibilities to target endogenous tumor-specific antigens.
人们已经充分认识到针对白血病和实体瘤等人类癌症开发新型治疗方法的必要性。人类T细胞有望在治疗方法上带来根本性变革。T细胞与肿瘤细胞的相互作用是一个关键事件，主要由T细胞受体（TCR）对HLA口袋中肽段的识别驱动。然而，在基于TCR的T细胞疗法中，要么TCR不匹配，要么主要组织相容性复合体密度低，导致肿瘤细胞逃避免疫反应。TCR分子具有低结合亲和力，阻碍了它们的识别。毫无疑问，抗体疗法是一种有效的癌症治疗方法。作为新一代单克隆抗体，TCR样抗体可以模拟TCR识别，但不易受到肿瘤逃避免疫反应机制的影响。作为T细胞表面表达的嵌合抗原受体（CAR）结构，TCR样抗体可以赋予T细胞抗原特异性。新型TCR样CAR对于推动过继性细胞疗法，特别是T细胞疗法的新技术可能很重要，并为靶向内源性肿瘤特异性抗原开辟了可能性。
