Abstract
Purpose: Limited expansion ability and cytotoxic function are major problems of using tumor-infiltrating lymphocytes (TILs) in vivo. We sought to determine whether adoptive transfer of autologous modified TILs mediates regression of advanced tumors.
Experimental Design: First, anti-tumor effects of switching PD-1 to CD28 signaling and anti-CD19 CAR-modified NY-ESO-1-TCR T cells (hereafter “PD-1-CD28 TCR-T” and “Anti-CD19 CAR-TCR-T” cells, respectively) were tested in vitro and in vivo. Furthermore, the safety and anti-tumor ability of S-TILs (TILs modified by transducing with anti-CD19 CAR and PD-1-CD28 vectors) were evaluated in vivo. PD-1-CD28 TCR-T cells produced formidable anti-tumor ability overcoming PD-1/PD-L1 signaling in vivo.
Results: Anti-CD19 CAR-TCR-T cells stimulated with CD19+ B cells exhibited powerful expansion and anti-tumor ability in vitro and in vivo. Three patients with refractory solid tumors received S-TIL infusion. There was no treatment-related mortality, and none of the patients experienced severe side effects. One patient with melanoma achieved a partial response and two patients with colon or kidney cancer achieved long-term stable disease following S-TIL therapy.
Conclusions: To our knowledge, this is the first report describing the safety and efficacy of adoptive transfer of autologous S-TILs to control disease in patients with advanced cancers, suggesting that S-TILs may be a promising alternative therapy for cancer treatment.
Citation Format: Xinfeng Chen, Xuan Zhao, Liping Wang, Weiyue Gu, Yi Zhang. PD-1-CD28-enhanced receptor and anti-CD19 CAR-modified tumor-infiltrating T lymphocytes produce potential anti-tumor ability in solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT144.
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