Chinese Journal of Cancer Research

, Volume 24, Issue 2, pp 143–150 | Cite as

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

  • 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
  • Tao Shen
  • Jun RenEmail author
Original Article Breast Cancer



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.

Key words

HER2-positive breast cancer Trastuzumab-resistant Dendritic cells Immunotherapy Reconstructive human adeno-association virus 


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Copyright information

© Chinese Anti-Cancer Association and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Xiao-lin Lin
    • 1
  • Xiao-li Wang
    • 1
  • Bo Ma
    • 1
  • Jun Jia
    • 1
  • Ying Yan
    • 1
  • Li-jun Di
    • 1
  • Yan-hua Yuan
    • 1
  • Feng-ling Wan
    • 1
  • Yuan-li Lu
    • 1
  • Xu Liang
    • 1
  • Tao Shen
    • 2
  • Jun Ren
    • 1
    Email author
  1. 1.Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Breast CancerPeking University Cancer Hospital & InstituteBeijingChina
  2. 2.Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of GeriatricsMinistry of HealthBeijingChina

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