光热疗法促进 CAR T 细胞浸润肿瘤并增强其抗肿瘤活性。
Photothermal Therapy Promotes Tumor Infiltration and Antitumor Activity of CAR T Cells.
机构信息
Department of Bioengineering, California NanoSystems Institute, Jonsson Comprehensive Cancer Center and Center for Minimally Invasive Therapeutics, University of California, Los Angeles, CA, 90095, USA.
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, 27695, USA.
出版信息
Adv Mater. 2019 Jun;31(23):e1900192. doi: 10.1002/adma.201900192. Epub 2019 Mar 27.
Chimeric antigen receptor (CAR)-redirected T lymphocytes (CAR T cells) show modest therapeutic efficacy in solid tumors. The desmoplastic structure of the tumor and the immunosuppressive tumor microenvironment usually account for the reduced efficacy of CAR T cells in solid tumors. Mild hyperthermia of the tumor reduces its compact structure and interstitial fluid pressure, increases blood perfusion, releases antigens, and promotes the recruitment of endogenous immune cells. Therefore, the combination of mild hyperthermia with the adoptive transfer of CAR T cells can potentially increase the therapeutic index of these cells in solid tumors. It is found that the chondroitin sulfate proteoglycan-4 (CSPG4)-specific CAR T cells infused in Nod scid gamma mice engrafted with the human melanoma WM115 cell line have superior antitumor activity after photothermal ablation of the tumor. The findings suggest that photothermal therapy facilitates the accumulation and effector function of CAR T cells within solid tumors.
嵌合抗原受体 (CAR)-靶向 T 淋巴细胞 (CAR T 细胞) 在实体瘤中的治疗效果有限。肿瘤的间质性结构和免疫抑制性肿瘤微环境通常是 CAR T 细胞在实体瘤中疗效降低的原因。肿瘤的轻度热疗可降低其致密结构和细胞间质内压，增加血液灌注，释放抗原，并促进内源性免疫细胞的募集。因此，将轻度热疗与 CAR T 细胞的过继转移相结合，可能会提高这些细胞在实体瘤中的治疗指数。研究发现，在荷人黑色素瘤 WM115 细胞系的 Nod scid gamma 小鼠中输注的软骨素硫酸盐蛋白聚糖-4 (CSPG4)-特异性 CAR T 细胞，在肿瘤光热消融后具有更好的抗肿瘤活性。这些发现表明，光热疗法有助于 CAR T 细胞在实体瘤中的积累和效应功能。
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