SCIENCE@home

Construction of self-driving anti-αFR CAR-engineered NK cells based on IFN-γ and TNF-α synergistically induced high expression of CXCL10

Min He,Xiang Ao,Yu Yang,Yanmin Xu,Tao Liu,Luoquan Ao,Wei Guo,W. Xing,Jing Xu,Cheng Qian,Jianhua Yu,Xiang Xu,Ping Yi

Published 2024 in Neoplasia

ABSTRACT

Highlights • In this study, we found for the first time that the third-generation αFR-CAR-NK92 effector cells targeting αFR successfully constructed in the previous stage of our research group can produce the chemokine CXCL10 after co-culture with ovarian cancer target cells, and no relevant studies have reported this phenomenon in CAR-T/NK cell therapy.• In ovarian cancer cells, we investigated the signaling pathway that TNF-α or/and IFN-γ induces the secretion of CXCL10, which was not been reported before.• In cancer cells, we studied the mechanism by which TNF-α and IFN-γ synergically induce the increase of CXCL10 secretion in cancer cells, which has not been reported before.• In this study, we used the CXCL10/CXCR3 axis for the first time to construct the fourth-generation CXCR3-αFR-CAR-NK92 cells that co-express the chemokine receptor CXCR3• We verified the killing function and chemotaxis of CXCR3-αFR-CAR-NK92 cells targeting ovarian cancer cells through in vitro and in vivo experiments.• The CXCR3-αFR-CAR-NK92 cells constructed by us improved the immunotherapy efficacy of αFR-CAR-NK92 cells, providing a new strategy for immunotherapy of ovarian cancer. In particular, it is beneficial to personalized treatment for this patient group of high-grade serous ovarian cancer immune response type (that is, tumor tissue high expression of CXCL10), and to a certain extent, alleviate the difficulty of transport obstruction when CAR-NK92 cells treat solid ovarian cancer.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-36 of 36 references · Page 1 of 1

CITED BY

Showing 1-13 of 13 citing papers · Page 1 of 1