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HER2-specific T lymphocytes kill both trastuzumab-resistant and trastuzumab-sensitive breast cell lines in vitro

Publication ,  Journal Article
Lin, XL; Wang, XL; Ma, B; Jia, J; Yan, Y; Di, LJ; Yuan, YH; Wan, FL; Lu, YL; Liang, X; Shen, T; Ren, J
Published in: Chinese Journal of Cancer Research
2012

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. 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. 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%). 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.

Duke Scholars

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Published In

Chinese Journal of Cancer Research

DOI

ISSN

1000-9604

Publication Date

2012

Volume

24

Start / End Page

143 / 150

Related Subject Headings

  • Oncology & Carcinogenesis
 

Citation

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Lin, X. L., Wang, X. L., Ma, B., Jia, J., Yan, Y., Di, L. J., … Ren, J. (2012). HER2-specific T lymphocytes kill both trastuzumab-resistant and trastuzumab-sensitive breast cell lines in vitro. Chinese Journal of Cancer Research, 24, 143–150. https://doi.org/10.1007/s11670-012-0143-6
Lin, X. L., X. L. Wang, B. Ma, J. Jia, Y. Yan, L. J. Di, Y. H. Yuan, et al. “HER2-specific T lymphocytes kill both trastuzumab-resistant and trastuzumab-sensitive breast cell lines in vitro.” Chinese Journal of Cancer Research 24 (2012): 143–50. https://doi.org/10.1007/s11670-012-0143-6.
Lin XL, Wang XL, Ma B, Jia J, Yan Y, Di LJ, et al. HER2-specific T lymphocytes kill both trastuzumab-resistant and trastuzumab-sensitive breast cell lines in vitro. Chinese Journal of Cancer Research. 2012;24:143–50.
Lin, X. L., et al. “HER2-specific T lymphocytes kill both trastuzumab-resistant and trastuzumab-sensitive breast cell lines in vitro.” Chinese Journal of Cancer Research, vol. 24, 2012, pp. 143–50. Manual, doi:10.1007/s11670-012-0143-6.
Lin XL, Wang XL, Ma B, Jia J, Yan Y, Di LJ, Yuan YH, Wan FL, Lu YL, Liang X, Shen T, Ren J. HER2-specific T lymphocytes kill both trastuzumab-resistant and trastuzumab-sensitive breast cell lines in vitro. Chinese Journal of Cancer Research. 2012;24:143–150.
Journal cover image

Published In

Chinese Journal of Cancer Research

DOI

ISSN

1000-9604

Publication Date

2012

Volume

24

Start / End Page

143 / 150

Related Subject Headings

  • Oncology & Carcinogenesis