Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran.
Adv Drug Deliv Rev. 2019 Feb 15;141:41-46. doi: 10.1016/j.addr.2019.04.006. Epub 2019 Apr 17.
Redirecting the recognition specificity of T lymphocytes to designated tumour cell surface antigens by transferring chimeric antigen receptor (CAR) genes is becoming an effective strategy to combat cancer. Today, CAR T-cell therapy has proven successful in the treatment of haematological malignancies and the first CD19 CAR T-cell products has already entered the market. This success is expanding CAR design for broader malignancies including solid tumours. Nevertheless, CARs such as those built on antigen-specific single chain antibody variable fragment (scFv) may induce some adverse effects. Here, we briefly review CAR T-cell bioengineering and discuss selected important initiatives for improved T-cell reprogramming, function and safety. In this respect, we further elaborate on unconventional CARs structured on single variable domain of heavy chain (VHH) antibodies (single-domain antibodies) as an alternative to scFv, because of their interesting immunological and physicochemical characteristics and unique structure, which shows a high degree of homology with human VH3 gene family.
通过转导嵌合抗原受体（CAR）基因来改变 T 淋巴细胞对特定肿瘤细胞表面抗原的识别特异性，正在成为一种对抗癌症的有效策略。如今，CAR T 细胞疗法已被证明在治疗血液恶性肿瘤方面取得了成功，首个 CD19 CAR T 细胞产品已进入市场。这一成功正在扩展 CAR 的设计，以涵盖更广泛的恶性肿瘤，包括实体瘤。然而，基于抗原特异性单链抗体可变片段（scFv）的 CAR 可能会引起一些不良反应。在这里，我们简要回顾了 CAR T 细胞的生物工程，并讨论了一些重要的举措，以改善 T 细胞的重编程、功能和安全性。在这方面，我们进一步阐述了基于重链（VHH）抗体（单域抗体）单一可变结构域的非传统 CAR，因为它们具有有趣的免疫学和物理化学特性以及独特的结构，与人类 VH3 基因家族具有高度同源性。
