Cancer immunotherapy using a potent immunodominant CTL epitope.

Abstract

Immunotherapy has emerged as a promising approach that can be used in conjunction with conventional chemotherapy and radiotherapy to further improve the survival rate of patients with advanced cancer. We have recently shown in previous studies that chemotherapy and radiation therapy can alter the tumor microenvironment and allow intratumoral vaccination to prime the adaptive immune system leading to the generation of antigen-specific cell-mediated immune responses. Here, we investigated whether intratumoral injection of a foreign immunodominant peptide (GP33) and the adjuvant CpG into tumors following cisplatin chemotherapy could lead to potent antitumor effects and antigen-specific cell-mediated immune responses. We observed that treatment with all three agents produced the most potent antitumor effects compared to pairwise combinations. Moreover, treatment with cisplatin, CpG and GP33 was able to control tumors at a distant site, indicating that our approach is able to induce cross-presentation of the tumor antigen. Treatment with cisplatin, CpG and GP33 also enhanced the generation of GP33-specific and E7-specific CD8+ T cells and decreased the number of MDSCs in tumor loci, a process found to be mediated by the Fas-FasL apoptosis pathway. The treatment regimen presented here represents a universal approach to cancer control.

• Authors: Liwen Song, Ming-Chieh Yang, Jayne Knoff, Zu-Yue Sun, T-C Wu, Chien-Fu Hung
• Journal: Vaccine (Vaccine) Vol. 32 Issue 46 Pg. 6039-48 (Oct 21 2014) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 25245934 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Antigens, Neoplasm
• CPG-oligonucleotide
• Cancer Vaccines
• Immunodominant Epitopes
• Oligodeoxyribonucleotides
• Papillomavirus E7 Proteins
• oncogene protein E7, Human papillomavirus type 16
• Cisplatin

Topics

• Animals
• Antigens, Neoplasm (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (immunology)
• Cisplatin (pharmacology)
• Cross-Priming
• Female
• Immunity, Cellular
• Immunodominant Epitopes (immunology)
• Immunotherapy
• Mice, Inbred C57BL
• Neoplasms, Experimental (immunology, therapy)
• Oligodeoxyribonucleotides (immunology)
• Papillomavirus E7 Proteins (immunology)