Department of Chemical and Biomolecular Engineering, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Department of Microbiology, Immunology, and Molecular Genetics, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Curr Opin Biotechnol. 2023 Dec;84:103020. doi: 10.1016/j.copbio.2023.103020. Epub 2023 Nov 16.
T cells engineered to express chimeric antigen receptors (CARs) have demonstrated robust response rates in treating hematological malignancies. However, solid tumors present multiple challenges that hinder the antitumor efficacy of CAR-T cells, including antigen heterogeneity, off-tumor and systemic toxicities, and the immunosuppressive milieu of the tumor microenvironment (TME). Notably, the TME of solid tumors is characterized by chemokine dysregulation and a dense architecture consisting of tumor stroma, extracellular matrix, and aberrant vasculature that impede migration of CAR-T cells to the tumor site as well as infiltration into the solid-tumor mass. In this review, we highlight recent advances to improve CAR-T-cell trafficking to and infiltration of solid tumors to promote effective antigen recognition by CAR-T cells.
经基因工程改造表达嵌合抗原受体（CAR）的 T 细胞在治疗血液恶性肿瘤方面显示出了强大的反应率。然而，实体瘤存在多种挑战，这些挑战会阻碍 CAR-T 细胞的抗肿瘤疗效，包括抗原异质性、脱靶毒性和全身毒性，以及肿瘤微环境（TME）的免疫抑制微环境。值得注意的是，实体瘤的 TME 表现为趋化因子失调以及由肿瘤基质、细胞外基质和异常血管组成的密集结构，这会阻碍 CAR-T 细胞向肿瘤部位的迁移以及向实体瘤肿块的浸润。在这篇综述中，我们强调了最近的进展，以改善 CAR-T 细胞向实体瘤的转移和浸润，从而促进 CAR-T 细胞对有效抗原的识别。
