Chimeric peptide containing both B and T cells epitope of tumor-associated antigen L6 enhances anti-tumor effects in HLA-A2 transgenic mice.

Abstract

Synthetic peptides are attractive for cancer immunotherapy because of their safety and flexibility. In this report, we identified a new B cell epitope of tumor-associated antigen L6 (TAL6) that could induce antibody-dependent cellular cytotoxicity (ADCC) in vivo. We incorporated the B cell epitope with a cytotoxic T lymphocyte (CTL) and a helper T (Th) epitope to form a chimeric long peptide. We formulated the chimeric peptide with different adjuvants to immunize HLA-A2 transgenic mice and evaluate their immunogenicity. The chimeric peptide formulated with an emulsion type nanoparticle (PELC) adjuvant and a toll-like receptor 9 agonist (CpG ODN) (PELC/CpG) induced the greatest ADCC and CTL responses. The induced anti-tumor immunity inhibited the growth of TAL6-positive cancer cells. Moreover, we observed that immunization with the chimeric peptide inhibited cancer cell migration in vitro and metastasis in vivo. These data suggest that a chimeric peptide containing both B and T cell epitopes of TAL6 formulated with PELC/CpG adjuvant is feasible for cancer immunotherapy.

• Authors: Su-I Lin, Ming-Hsi Huang, Yu-Wen Chang, I-Hua Chen, Steve Roffler, Bing-Mae Chen, Yuh-Pyng Sher, Shih-Jen Liu
• Journal: Cancer letters (Cancer Lett) Vol. 377 Issue 2 Pg. 126-33 (07 28 2016) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 27130449 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• Antigens, Neoplasm
• Cancer Vaccines
• Epitopes, B-Lymphocyte
• Epitopes, T-Lymphocyte
• HLA-A2 Antigen
• Oligodeoxyribonucleotides
• Recombinant Fusion Proteins
• Tlr9 protein, mouse
• Toll-Like Receptor 9
• Vaccines, Synthetic

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Antibody-Dependent Cell Cytotoxicity
• Antigens, Neoplasm (administration & dosage, immunology)
• Cancer Vaccines (administration & dosage, immunology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Epitopes, B-Lymphocyte (administration & dosage, immunology)
• Epitopes, T-Lymphocyte (administration & dosage, immunology)
• Female
• HLA-A2 Antigen (genetics, immunology, metabolism)
• Immunization
• Melanoma, Experimental (immunology, metabolism, secondary, therapy)
• Mice, Inbred C57BL
• Mice, Transgenic
• Oligodeoxyribonucleotides (administration & dosage, immunology)
• Recombinant Fusion Proteins (administration & dosage, immunology)
• Skin Neoplasms (immunology, metabolism, pathology, therapy)
• T-Lymphocytes, Cytotoxic (immunology, metabolism)
• T-Lymphocytes, Helper-Inducer (immunology, metabolism)
• Time Factors
• Toll-Like Receptor 9 (agonists, immunology, metabolism)
• Transfection
• Tumor Burden
• Vaccines, Synthetic (administration & dosage, immunology)