Immunization with a plasmid DNA vaccine encoding the N-terminus of Insulin like Growth Factor Binding Protein-2 in advanced ovarian cancer leads to high level Type I immune responses.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Denise L CecilMary L Disis

Abstract

Cancer vaccines targeting nonmutated proteins elicit limited Type I T-cell responses and can generate T-regulatory and Type II T-cells. Class II epitopes that selectively elicit Type I or Type II cytokines can be identified in nonmutated cancer associated proteins. In mice, a T-helper I selective IGFBP-2 N-terminus vaccine generated high levels of IFN-Ɣ secreting T-cells, no regulatory T-cells and significant anti-tumor activity. We conducted a Phase I trial of Th1 selective IGFBP-2 vaccination in patients with advanced ovarian cancer. Twenty-five patients were enrolled. The IGFBP-2 N-terminus plasmid-based vaccine was administered monthly for three months. Toxicity was graded by NCI criteria and antigen specific T-cells measured by IFN-Ɣ/IL-10 ELISPOT. T-cell diversity and phenotype were assessed. The vaccine was well tolerated, 99% of adverse events graded 1 or 2, and generated high levels of IGFBP-2 IFN-Ɣ secreting T-cells in 50% of patients. Both Tbet+ CD4 (p=0.04) and CD8 (p=0.007) T-cells were significantly increased in immunized patients. There was no increase in GATA3+ CD4 or CD8, IGFBP-2 IL-10 secreting T-cells or T-regulatory cells. A significant increase in T-cell clonality occurred in immunized patients (p=0.03, pre...Continue Reading

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