Therapeutic effect of a T helper cell supported CTL response induced by a survivin peptide vaccine against murine cerebral glioma

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2008-12, Vol.57 (12), p.1827-1835
• Main Authors: Ciesielski, Michael J., Kozbor, Danuta, Castanaro, Carla A., Barone, Tara A., Fenstermaker, Robert A.
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Antigens; Antineoplastic agents; Biological and medical sciences; Brain Neoplasms - immunology; Brain Neoplasms - therapy; Cancer Research; Cancer therapies; Cancer vaccines; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; Cytokines; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - transplantation; Epitopes, T-Lymphocyte - immunology; Flow Cytometry; Glioma - immunology; Glioma - therapy; Histocompatibility Antigens - genetics; Histocompatibility Antigens - immunology; Immunology; Immunotherapy; Inhibitor of Apoptosis Proteins; Ligands; Lymphocytes; Male; Medical prognosis; Medical sciences; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Microtubule-Associated Proteins - immunology; Neoplasm Proteins - immunology; Neurology; Oncology; Original Article; Peptides; Pharmacology. Drug treatments; T cell receptors; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Helper-Inducer - immunology; Tumors of the nervous system. Phacomatoses; Vaccines, Subunit - immunology; Vaccines, Subunit - therapeutic use
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-008-0510-9

Survivin is a tumor-associated antigen (TAA) that has significant potential for use as a cancer vaccine target. To identify survivin epitopes that might serve as targets for CTL-mediated, anti-tumor responses, we evaluated a series of survivin peptides with predicted binding to mouse H2-K b and human HLA-A*0201 antigens in peptide-loaded dendritic cell (DC) vaccines. H2-K b -positive, C57BL/6 mice were vaccinated using syngeneic, peptide-loaded DC2.4 cells. Splenocytes from vaccinated mice were screened by flow cytometry for binding of dimeric H2-K b :Ig to peptide-specific CD8+ T cells. Two survivin peptides (SVN 57–64 and SVN 82–89 ) generated specific CD8+ T cells. We chose to focus on the SVN 57–64 peptide because that region of the molecule is 100% homologous to human survivin. A larger peptide (SVN 53–67 ), containing multiple class I epitopes, and a potential class II ligand, was able to elicit both CD8+ CTL and CD4+ T cell help. We tested the SVN 53–67 15-mer peptide in a therapeutic model using a peptide-loaded DC vaccine in C57BL/6 mice with survivin-expressing GL261 cerebral gliomas. This vaccine produced significant CTL responses and helper T cell-associated cytokine production, resulting in a significant prolongation of survival. The SVN 53–67 vaccine was significantly more effective than the SVN 57–64 core epitope as a cancer vaccine, emphasizing the potential benefit of incorporating multiple class I epitopes and associated cytokine support within a single peptide.