Photothermal Therapy Promotes Tumor Infiltration and Antitumor Activity of CAR T Cells. Issue 23 (27th March 2019)

• Record Type: Journal Article
• Authors: Chen, Qian; Hu, Quanyin; Dukhovlinova, Elena; Chen, Guojun; Ahn, Sarah; Wang, Chao; Ogunnaike, Edikan A.; Ligler, Frances S.; Dotti, Gianpietro; Gu, Zhen
• Is Part Of: Advanced materials. Volume 31:Issue 23(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-03-27
• Subjects: CAR T cells -- cell therapy -- drug delivery -- immunotherapy -- photothermal therapy; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adma.201900192
• Languages: English
• ISSNs: 0935-9648

Abstract

Abstract: 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. Abstract : Photothermal ablation of tumors is demonstrated to promote the therapeutic efficacy of chimeric antigen receptor (CAR) T cells. Mild hyperthermia can promote direct tumor cell killing, partially disrupt the extracellular matrix, decrease the interstitial fluid pressure, and increase local blood perfusion. All these modifications caused by photothermal therapy ultimately promote the infiltration and antitumor effects of adoptively transferred CAR T cells.