嵌合抗原受体（CAR）T 细胞疗法呈现出显着的效果，特别是对于血液恶性肿瘤的治疗。然而，要在实体瘤的治疗中取得类似的成功，还需要克服一些限制和挑战。这些挑战涉及靶点的选择、肿瘤微环境的渗透以及功能的维持。肿瘤血管系统是白细胞进入肿瘤实质的主要屏障。由于肿瘤进展过程中脉管系统暴露于血管生成因子，内皮细胞对炎性细胞因子变得无反应，导致白细胞粘附分子表达减少。由于此类粘附分子是白细胞外渗的先决条件，内皮细胞无反应性使肿瘤能够逃避内源性免疫以及 CAR T 细胞等细胞免疫疗法。因此，克服内皮细胞无反应性，例如通过施用血管生成抑制剂，被认为可以恢复抗肿瘤免疫力。与此同时，内源性免疫细胞以及 CAR T 细胞等细胞疗法都可以渗透到肿瘤实质中。在这里，我们讨论了抗血管生成药物的先前或伴随治疗如何改善 CAR T 细胞疗法，成为治疗实体瘤的有吸引力的策略。版权所有 © 2024。由 Elsevier B.V. 出版。

Chimeric antigen receptor (CAR) T cell therapy presents significant results, especially for the treatment of hematologic malignancies. However, there are limitations and challenges to be overcome to achieve similar success for the treatment of solid tumors. These challenges involve selection of the target, infiltration into the tumor microenvironment and maintenance of functionality. The tumor vasculature is a major barrier for leukocytes to enter the tumor parenchyma. Due to the exposure of the vasculature to angiogenic growth factors during tumor progression, the endothelial cells become anergic to inflammatory cytokines, resulting in reduced leukocyte adhesion molecule expression. As such adhesion molecules are a prerequisite for leukocyte extravasation, endothelial cell anergy allows tumors to escape from endogenous immunity, as well as from cellular immunotherapies such as CAR T cells. Hence, overcoming endothelial cell anergy, e.g. through the administration of angiogenesis inhibitors, is believed to restore anti-tumor immunity. Concomitantly, both endogenous immune cells as well as cellular therapeutics such as CAR T cells can permeate into the tumor parenchyma. Here, we discuss how prior or concomitant treatment with an antiangiogenic drug can improve CAR T cell therapy, to become an attractive strategy for the treatment of solid tumors.Copyright © 2024. Published by Elsevier B.V.