Malignant gliomas are among the most devastating of all human cancers. Even with aggressive treatment, including surgery, radiation therapy, and chemotherapy survival remains poor. Survivin is a tumor-associated antigen that is highly expressed in many cancers and is associated with chemotherapy resistance, increased tumor recurrence, and shorter patient survival. These features of the protein have made it an attractive target for vaccination strategies.
Researchers at Roswell Park Comprehensive Cancer Center have developed a peptide “molecular mimic” vaccine based on the survivin protein that is immunogenic in humans. Unlike other survivin based vaccine technologies, this peptide mimic elicits both CD8+ T cells and CD4+ T cell support targeted against tumor cells. This peptide is a 15 amino acid long epitope corresponding to AA53-AA67 of wild type survivin sequence. Roswell researchers have engineered an artificial replacement of AA57 (Cysteine to Methionine) and formulated the vaccine for delivery as a KLH conjugated peptide in adjuvant. As a result of this change, the peptide exhibits enhanced immunogenicity resulting in a strong immune response against human glioma cells. The “mimic” peptide contains several CTL epitopes with relatively limited HLA restriction and a Helper T cell epitope all designed within a single peptide, the change of C>M allows for enhanced presentation of these epitopes to the immune system and thus a more robust downstream immune response.
Ciesielski MJ, Ahluwalia MS, Munich SA, Orton M, Barone T, Chanan-Khan A, Fenstermaker RA. Antitumor cytotoxic T-cell response induced by a survivin peptide mimic. Cancer Immunology, Immunotherapy, 2010; 598:1211-1221
Fenstermaker RA, Ciesielski MJ. Challenges in the development of a survivin vaccine (SurVaxM) for malignant glioma. Expert Rev Vaccines, 2014; 13:377-85.