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.
Highlights
Lung cancer is one of the leading causes of malignancy-related death because of its frequency and its highly metastatic potential
To determine whether tumor associated antigen L6 (TAL6) protein was overexpressed in lung cancer cells as a tumor specific antigen for treatment, lung cancer cell lines and primary lung tumor tissues from NSCLC patients were stained with an anti-TAL6 monoclonal antibody
TAL6 was considered as a target for antibody-based immunotherapy against breast and lung cancer during the past decade, the therapeutic effects of TAL6 antibody-based immunotherapy are limited in humans
Summary
Lung cancer is one of the leading causes of malignancy-related death because of its frequency and its highly metastatic potential. Immunotherapy for lung cancer is considered as a promising treatment capable of inducing systemic tumor-specific immune responses without provoking serious side effects [1, 2]. The tumor-associated antigen L6 (TAL6), is a tumor-specific antigen which is a distant member of the transmembrane-4 superfamily (TM4SF) and is often overexpressed in human lung, breast, and colon cancer tissues but not in normal tissues [3,4,5]. The multi-peptides vaccine (IDM-2101) was designed to induce CTLs against five tumor-associated antigens (TAAs) frequently overexpressed in NSCLC (i.e. carconoembryonic antigen www.impactjournals.com/oncotarget (CEA), p53, Her, and melanoma antigens (MAGE)), and it provided clinical efficacy in metastatic NSCLC [16]
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