Intraperitoneal administration of carcinoembryonic antigen-directed chimeric antigen receptor T cells is a robust delivery route for effective treatment of peritoneal carcinomatosis from colorectal cancer in pre-clinical study

• Published in: Cytotherapy (Oxford, England) Vol. 26; no. 2; pp. 113 - 125
• Main Authors: Qian, Siyuan, Chen, Jun, Zhao, Yongchun, Zhu, Xiuxiu, Dai, Depeng, Qin, Lei, Hong, Juan, Xu, Yanming, Yang, Zhi, Li, Yunyan, Guijo, Ismael, Jiménez-Galanes, Santos, Guadalajara, Héctor, García-Arranz, Mariano, García-Olmo, Damián, Shen, Junjie, Villarejo-Campos, Pedro, Qian, Cheng
• Format: Journal Article
• Language: English
• Published: England 01.02.2024
• Subjects: Animals; Carcinoembryonic Antigen; Colorectal Neoplasms - pathology; Colorectal Neoplasms - therapy; Immunotherapy, Adoptive; Male; Neoplasm Recurrence, Local; Peritoneal Neoplasms - therapy; Receptors, Chimeric Antigen; T-Lymphocytes; Carcinoembryonic Antigen; CAR T cells; CAR T-cell expansion and distribution; Immunotherapy; Animal Models; Peritoneal Carcinomatosis
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2023.10.007

Peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is a highly challenging disease to treat. Systemic chimeric antigen receptor (CAR) T cells have shown impressive efficacy in hematologic malignancies but have been less effective in solid tumors. We explored whether intraperitoneal (i.p.) administration of CAR T cells could provide an effective and robust route of treatment for PC from CRC. We generated second-generation carcinoembryonic antigen (CEA)-specific CAR T cells. Various animal models of PC with i.p. and extraperitoneal metastasis were treated by i.p. or intravenous (i.v.) administration of CEA CAR T cells. Intraperitoneally administered CAR T cells exhibited superior anti-tumor activity compared with systemic i.v. cell infusion in an animal model of PC. In addition, i.p. administration conferred a durable effect and protection against tumor recurrence and exerted strong anti-tumor activity in an animal model of PC with metastasis in i.p. or extraperitoneal organs. Moreover, compared with systemic delivery, i.p. transfer of CAR T cells provided increased anti-tumor activity in extraperitoneal tumors without PC. This phenomenon was further confirmed in an animal model of pancreatic carcinoma after i.p. administration of our newly constructed prostate stem cell antigen-directed CAR T cells. Taken together, our data suggest that i.p. administration of CAR T cells may be a robust delivery route for effective treatment of cancer.