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.
Cytotherapy
; 26(2): 113-125, 2024 Feb.
Article
in En
| MEDLINE
| ID: mdl-37999667
ABSTRACT
BACKGROUND AIMS:
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.METHODS:
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.RESULTS:
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.CONCLUSIONS:
Taken together, our data suggest that i.p. administration of CAR T cells may be a robust delivery route for effective treatment of cancer.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peritoneal Neoplasms
/
Colorectal Neoplasms
/
Receptors, Chimeric Antigen
Limits:
Animals
Language:
En
Journal:
Cytotherapy
Journal subject:
TERAPEUTICA
Year:
2024
Document type:
Article