HER2-specific T lymphocytes kill both trastuzumab-resistant and trastuzumab-sensitive breast cell lines in vitro.
OBJECTIVE
Although the development of trastuzumab has improved the outlook for women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, the resistance to anti-HER2 therapy is a growing clinical dilemma. We aim to determine whether HER2-specific T cells generated from dendritic cells (DCs) modified with HER2 gene could effectively kill the HER2-positive breast cancer cells, especially the trastuzumab-resistant cells.


METHODS
The peripheral blood mononuclear cells (PBMCs) from healthy donors, whose HLA haplotypes were compatible with the tumor cell lines, were transfected with reconstructive human adeno-association virus (rhAAV/HER2) to obtain the specific killing activities of T cells, and were evaluated by lactate dehydrogenase (LDH) releasing assay.


RESULTS
Trastuzumab produced a significant inhibiting effect on SK-BR-3, the IC50 was 100ng/ml. MDA-MB-453 was resistant to trastuzumab even at a concentration of 10,000 ng/ml in vitro. HER2-specific T lymphocytes killed effectively SK-BR-3 [(69.86±13.41)%] and MDA-MB-453 [(78.36±10.68)%] at 40:1 (effector:target ratio, E:T), but had no significant cytotoxicity against HER2-negative breast cancer cell lines MDA-MB-231 or MCF-7 (less than 10%).


CONCLUSIONS
The study showed that HER2-specific T lymphocytes generated from DCs modified by rhAAV/HER2 could kill HER2-positive breast cancer cell lines in a HER2-dependent manner, and result in significantly high inhibition rates on the intrinsic trastuzumab-resistant cell line MDA-MB-453 and the tastuzumab-sensitive cell line SK-BR-3. These results imply that this immunotherapy might be a potential treatment to HER2-positive breast cancer.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Breast Cancer, Peking University Cancer Hospital & Institute, Beijing 100142, China;
Xiao-Lin
XL
Lin
Xiao-Li
XL
Wang
Bo
B
Ma
Jun
J
Jia
Ying
Y
Yan
Li-Jun
LJ
Di
Yan-Hua
YH
Yuan
Feng-Ling
FL
Wan
Yuan-Li
YL
Lu
Xu
X
Liang
Tao
T
Shen
Jun
J
Ren
Dendritic cells; HER2-positive breast cancer; Immunotherapy; Reconstructive human adeno-association virus; Trastuzumab-resistant