Construction of CAR-T cells targeting TM4SF1 and its anti-tumor capacity in ovarian cancer

Yijie Shen; Guodi Liu; Qian Zhang; Xiaoli Tian; Liming Ouyang; Lixin Zhang

doi:10.1016/j.imlet.2023.01.011

Construction of CAR-T cells targeting TM4SF1 and its anti-tumor capacity in ovarian cancer

Immunol Lett. 2023 Mar:255:1-9. doi: 10.1016/j.imlet.2023.01.011. Epub 2023 Feb 3.

Authors

Yijie Shen¹, Guodi Liu², Qian Zhang³, Xiaoli Tian⁴, Liming Ouyang⁵, Lixin Zhang¹

Affiliations

¹ State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
² State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China; Shanghai Yihao Biological Technology Co., Ltd., Shanghai, 200231, China.
³ Shanghai Yihao Biological Technology Co., Ltd., Shanghai, 200231, China.
⁴ State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China; Shanghai Yihao Biological Technology Co., Ltd., Shanghai, 200231, China. Electronic address: ceo@shmlrs.cn.
⁵ State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China. Electronic address: ouyanglm@ecust.edu.cn.

PMID: 36739093
DOI: 10.1016/j.imlet.2023.01.011

Abstract

Ovarian cancer (OC) is the most lethal gynecological malignancy with a 5-year survival rate of 49.1% on average. In clinical practice, cytoreduction and chemotherapy remain the conventional treatment for advanced OC. However, the overall prognosis remains poor, which urges oncologists to develop new treatments. Chimeric antigen receptor (CAR)-T therapy as a branch of immunotherapy had gained a success in treating hematological malignancies. TM4SF1, a potential biomarker in many tumors, was validated highly expressed in ovarian cancer. Here we constructed a 3^rd generation CAR-T agent targeting TM4SF1 to treat ovarian cancer. CAR-T cells showed a specific cytotoxicity against TM4SF1 positive tumor cell lines in vitro and repressed SKOV3-derived tumor growth in vivo. This is the first time reporting a CAR-T therapy targeting TM4SF1 in ovarian cancer. Our results suggested that TM4SF1 could be a very promising target in curing OC and showed the possibility of TM4SF1-based immunotherapy.

Keywords: CAR-T therapy; Immunotherapy; Ovarian cancer; TM4SF1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Surface / metabolism
Cell Line, Tumor
Female
Humans
Immunotherapy
Immunotherapy, Adoptive / methods
Neoplasm Proteins / metabolism
Ovarian Neoplasms* / pathology
Ovarian Neoplasms* / therapy
Receptors, Chimeric Antigen*
T-Lymphocytes

Substances

Receptors, Chimeric Antigen
TM4SF1 protein, human
Antigens, Surface
Neoplasm Proteins