CAR-T过继细胞治疗靶向治疗实体肿瘤的挑战

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Adoptive therapy with CAR redirected T cells: the challenges in targeting solid tumors.

Recent spectacular success in the adoptive cell therapy of leukemia and lymphoma with chimeric antigen receptor (CAR)-modified T cells raised the expectations that this therapy may be efficacious in a wide range of cancer entities. The expectations are based on the predefined specificity of CAR T cells by an antibody-derived binding domain that acts independently of the natural T-cell receptor, recognizes targets independently of presentation by the major histocompatibility complex and allows targeting toward virtually any cell surface antigen. We here discuss that targeting CAR T cells toward solid tumors faces certain circumstances critical for the therapeutic success. Targeting tumor stroma and taking advantage of TRUCK cells, in other words, CAR T cells with inducible release of a transgenic payload, are some strategies envisaged to overcome current limitations in the near future.

KEYWORDS:

CAR; T cell; adoptive cell therapy; cancer; chimeric antigen receptor; gene transfer

CAR-T过继细胞治疗靶向治疗实体肿瘤的挑战

近期过继CAR-T细胞治疗技术在白血病和淋巴细胞白血病的治疗中取得的成功，唤起了人们拓展这种技术可能在更多的实体肿瘤治疗中应用的期望。这种期望基于CAR-T的特异性，通过表达一种独立于天然T细胞的抗体衍生的结合域，它几乎能够针对细胞表面的任何抗原。这篇文章中，我们讨论了某些情况下，靶向CAR-T细胞治疗实体肿瘤成功的关键。靶向肿瘤的基质环境和利用TRUCK细胞，换句话说，使用转基因有效负荷的诱导释放，是不久的将来，克服目前局限性的一些战略设想。

关键词：

CAR; T cell; adoptive cell therapy; cancer; chimeric antigen receptor; gene transfer

CAR；细胞；细胞疗法；肿瘤；嵌合抗原受体；基因转移

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