Oncotarget

Research Papers:

A HLA-A2-restricted CTL epitope induces anti-tumor effects against human lung cancer in mouse xenograft model

Yuh-Pyng Sher, Su-I Lin, I-Hua Chen, Hsin-Yu Liu, Chen-Yuan Lin, I-Ping Chiang, Steve Roffler, Hsin-Wei Chen and Shih-Jen Liu _

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Oncotarget. 2016; 7:671-683. https://doi.org/10.18632/oncotarget.6400

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Abstract

Yuh-Pyng Sher1,3,*, Su-I Lin6,7,*, I-Hua Chen6, Hsin-Yu Liu6, Chen-Yuan Lin4, I-Ping Chiang5, Steve Roffler8, Hsin-Wei Chen2,6, Shih-Jen Liu2,6,7

1Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan

2Graduate Institute of Immunology, China Medical University, Taichung, Taiwan

3Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan

4Division of Hematology and Oncology, China Medical University Hospital, Taichung, Taiwan

5Department of Pathology, China Medical University Hospital, Taichung, Taiwan

6National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan

7Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan

8Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Shih-Jen Liu, e-mail: [email protected]

Keywords: peptide, cytotoxic T lymphocytes, TAL6, lung cancer

Received: May 02, 2015     Accepted: November 16, 2015     Published: November 26, 2015

ABSTRACT

Cancer immunotherapy is attractive for antigen-specific T cell-mediated anti-tumor therapy, especially in induction of cytotoxic T lymphocytes. In this report, we evaluated human CTL epitope-induced anti-tumor effects in human lung cancer xenograft models. The tumor associated antigen L6 (TAL6) is highly expressed in human lung cancer cell lines and tumor specimens as compared to normal lung tissues. TAL6 derived peptides strongly inhibited tumor growth, cancer metastasis and prolonged survival time in HLA-A2 transgenic mice immunized with a formulation of T-helper (Th) peptide, synthetic CpG ODN, and adjuvant Montanide ISA-51 (ISA-51). Adoptive transfer of peptide-induced CTL cells from HLA-A2 transgenic mice into human tumor xenograft SCID mice significantly inhibited tumor growth. Furthermore, combination of CTL-peptide immunotherapy and gemcitabine additively improved the therapeutic effects. This pre-clinical evaluation model provides a useful platform to develop efficient immunotherapeutic drugs to treat lung cancer and demonstrates a promising strategy with benefit of antitumor immune responses worthy of further development in clinical trials.


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