Antitumor cytotoxic T-cell response induced by a survivin peptide mimic

Michael J. Ciesielski, Manmeet S. Ahluwalia, Stephan A. Munich, Molly Orton, Tara Barone, Asher A Chanan Khan, Robert A. Fenstermaker

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Survivin is a tumor-associated antigen with significant potential as a cancer vaccine target. We have identified a survivin peptide mimic containing human MHC class I epitopes and a potential class II ligand that induces a potent antitumor response in C57BL/6 mice with GL261 cerebral gliomas. This peptide is able to elicit both CD8+ CTL and T helper cell responses in C57BL/6 mice. The corresponding region of the human survivin molecule represented by peptide SVN53-67 is 100% homologous to the murine protein, but SVN53-67 is weakly immunogenic in man. We evaluated several amino acid substitutions in putative human MHC I anchor positions in SVN53-67 to identify potential peptide mimics that could provide an enhanced antitumor immune response against human glioma and primary central nervous system lymphoma (PCNSL) cells in culture. We evaluated survivin peptides with predicted binding to human HLA-A*0201 antigen using peptide-loaded dendritic cells from PBMC of patients with these malignancies. One alteration (M57) led to binding to HLA-A*0201 with significantly higher affinity. We compared the ability of autologous dendritic cells loaded with SVN53-67 peptide and SVN53-67/M57 in CTL assays against allomatched and autologous, survivin-expressing, human malignant glioma and PCNSL cells. Both SVN53-67 and SVN53-67/M57 produced CTL-mediated killing of malignant target cells; however, SVN53-67/M57 was significantly more effective than SVN53-67. Thus, SVN53-67/M57 may act as a peptide mimic to induce an enhanced antitumor CTL response in tumor patients. The use of SVN53-67/M57 as a cancer vaccine might have application for cancer vaccine therapy.

Original languageEnglish (US)
Pages (from-to)1211-1221
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume59
Issue number8
DOIs
StatePublished - Aug 2010
Externally publishedYes

Fingerprint

T-Lymphocytes
Peptides
Cancer Vaccines
Glioma
Inbred C57BL Mouse
Dendritic Cells
Lymphoma
Central Nervous System
Active Immunotherapy
Neoplasm Antigens
Amino Acid Substitution
Helper-Inducer T-Lymphocytes
Epitopes
Neoplasms
Cell Culture Techniques
Ligands
Proteins
HLA-A*02:01 antigen

Keywords

  • Antigen
  • Glioma
  • Peptide
  • Survivin
  • Tumor
  • Vaccine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy

Cite this

Ciesielski, M. J., Ahluwalia, M. S., Munich, S. A., Orton, M., Barone, T., Chanan Khan, A. A., & Fenstermaker, R. A. (2010). Antitumor cytotoxic T-cell response induced by a survivin peptide mimic. Cancer Immunology, Immunotherapy, 59(8), 1211-1221. https://doi.org/10.1007/s00262-010-0845-x

Antitumor cytotoxic T-cell response induced by a survivin peptide mimic. / Ciesielski, Michael J.; Ahluwalia, Manmeet S.; Munich, Stephan A.; Orton, Molly; Barone, Tara; Chanan Khan, Asher A; Fenstermaker, Robert A.

In: Cancer Immunology, Immunotherapy, Vol. 59, No. 8, 08.2010, p. 1211-1221.

Research output: Contribution to journalArticle

Ciesielski, MJ, Ahluwalia, MS, Munich, SA, Orton, M, Barone, T, Chanan Khan, AA & Fenstermaker, RA 2010, 'Antitumor cytotoxic T-cell response induced by a survivin peptide mimic', Cancer Immunology, Immunotherapy, vol. 59, no. 8, pp. 1211-1221. https://doi.org/10.1007/s00262-010-0845-x
Ciesielski, Michael J. ; Ahluwalia, Manmeet S. ; Munich, Stephan A. ; Orton, Molly ; Barone, Tara ; Chanan Khan, Asher A ; Fenstermaker, Robert A. / Antitumor cytotoxic T-cell response induced by a survivin peptide mimic. In: Cancer Immunology, Immunotherapy. 2010 ; Vol. 59, No. 8. pp. 1211-1221.
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