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

  • Original Article
  • Breast Cancer
  • Published:
Chinese Journal of Cancer Research

Abstract

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%).

Conclusion

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.

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Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Breast Cancer, Peking University Cancer Hospital & Institute, Beijing, 100142, China

    Xiao-lin Lin, Xiao-li Wang, Bo Ma, Jun Jia, Ying Yan, Li-jun Di, Yan-hua Yuan, Feng-ling Wan, Yuan-li Lu, Xu Liang & Jun Ren

  2. Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing, 100730, China

    Tao Shen

Authors
  1. Xiao-lin Lin
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  2. Xiao-li Wang
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  3. Bo Ma
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  4. Jun Jia
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  5. Ying Yan
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  6. Li-jun Di
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  7. Yan-hua Yuan
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  8. Feng-ling Wan
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  9. Yuan-li Lu
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  10. Xu Liang
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  11. Tao Shen
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  12. Jun Ren
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Corresponding author

Correspondence to Jun Ren.

Additional information

This work was supported by the grant from the National “973” Basic Research Program of China (No.2009CB521703) and Medical Oncology Leadership of Beijing Municipal Government Health Burean (No. 2009-2-16).

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Lin, Xl., Wang, Xl., Ma, B. et al. HER2-specific T lymphocytes kill both trastuzumab-resistant and trastuzumab-sensitive breast cell lines in vitro . Chin. J. Cancer Res. 24, 143–150 (2012). https://doi.org/10.1007/s11670-012-0143-6

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  • DOI: https://doi.org/10.1007/s11670-012-0143-6

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