We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
T cells expressing a HER2-specific chimeric antigen receptor as treatment for breast cancer.
- Authors
Xie, Xinshan; Li, Xiaobin; Liu, Gang; Zhao, Hui; Zhou, Zhenlong; Xiong, Sheng
- Abstract
Purpose: Human endothelial growth factor receptor-2 (HER2) is a leucine kinase receptor that is closely related to cell growth and differentiation. It is very weakly expressed in a few epithelial cells in normal tissue. Abnormal expression of HER2 usually leads to sustained activation of downstream signaling pathways, enabling epithelial cell growth, proliferation, and differentiation; this disturbs normal physiological processes and causes tumor formation. Overexpression of HER2 is related to the occurrence and development of breast cancer. HER2 has become a well-established immunotherapy target for breast cancer. We chose to construct a second-generation CAR targeting HER 2 to test whether it kills breast cancer. Methods: We constructed a second-generation CAR molecule targeting HER2, and we generated cells expressing this second-generation CAR through lentivirus infection of T lymphocytes. LDH assay and flow cytometry were perform to detect the effect of cells and animal models. Results: The result indicated that the CARHER2 T cells could selectively kill cells with high Her2 expression. The PBMC-activated/CARHer2 cells had stronger in vivo tumor suppressive activity than PBMC-activated cells, and administration of PBMC-activated/CARHer2 cells significantly improved the survival of tumor-bearing mice, and induced the production of more Th1 cytokines in tumor-bearing NSG mice. Conclusions: We prove that the generated T cells carrying the second-generation CARHer2 molecule could effectively guide immune effector cells to identify and kill HER2-positive tumor cells and inhibit tumors in model mice.
- Subjects
CHIMERIC antigen receptors; T cells; BREAST cancer; LEUCINE; ENDOTHELIAL growth factors; T cell receptors; LENTIVIRUS diseases
- Publication
Journal of Cancer Research & Clinical Oncology, 2023, Vol 149, Issue 13, p11561
- ISSN
0171-5216
- Publication type
Article
- DOI
10.1007/s00432-023-04996-5