Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 25, No 18S (June 20 Supplement), 2007: 3070
© 2007 American Society of Clinical Oncology

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Abstract

Presence of survivin-specific cytotoxic T-lymphocytes (CTLs) in pancreatic cancer patients, and specific killing of human pancreatic carcinoma cells in vitro by survivin-specific CTLs

MD Anderson Cancer Ctr, Houston, TX

3070

Background: The apoptosis inhibitor protein Survivin is an attractive target for a cancer vaccine because of its differential overexpression by most human tumors, its importance for tumor survival, and its demonstrated immunogenicity. To examine Survivin’s potential as a vaccine target for pancreatic cancer (PC), we evaluated the presence of Survivin-specific cytotoxic T-lymphocytes (CTLs) in PC patients and assessed the specific killing of HLA-A*0201+ human pancreatic carcinoma cell lines in vitro by Survivin-specific CTL. Methods: Mononuclear cells from the peripheral blood (PBMC) of PC patients and normal donors and Survivin peptides were used to generate Survivin-specific CTLs in vitro. The presence of Survivin-specific CTLs was evaluated by IFN- ELISPOT analysis. Recognition of human PC cell lines (e.g., Panc-1 and CF-Pac-1) was analyzed by ⁵¹Cr release assays. Results: Multiple CTL lines were generated from different donors against a number of Survivin 9-mer and 10-mer peptides, including Sur5–14, Sur95–104, and Sur96–104 and altered forms of these peptides with enhanced HLA-A*0201 binding. Sur5–14 (TLPPAWQPFL) and new modified mSur95–104 (ELMLGEFLKL) peptides could generate specific CTL from the PBMC of most donors, and the resulting CTL showed cytotoxicity against Survivin peptide-pulsed Panc-1 and CF-Pac-1 in an HLA-A2-dependent manner. We found for the first time that mSur95–104 could elicit CTL activity that cross-reacted with wild-type peptide and 9-mer Sur96–104 in IFN- ELISPOT assays. In our preliminary analysis, we detected Survivin peptide-specific CTLs in four of five PC patients for Sur5–14 and three of five for mSur95–104. All five PC patients had a positive response to a pool of A2 peptides as positive controls, indicating their immune competence. Conclusions: CTLs specific for human Survivin peptide Sur5–14 and the modified peptides mSur95–104 were detected in majority of the PC patients tested. Further, Survivin-specific CTLs killed pancreatic carcinoma cell lines in vitro. Our results suggest that these two peptides are potential vaccines for the treatment of PC.

No significant financial relationships to disclose.

Abstract presentation from the 2007 ASCO Annual Meeting