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Humoral Responses to Peptides Correlate with Overall Survival in Advanced Cancer Patients Vaccinated with Peptides Based on Pre-existing, Peptide-Specific Cellular Responses

¹ Departments of Immunology, ² Surgery, ³ Urology, ⁴ First Internal Medicine, ⁵ Gynecology, ⁶ Dermatology, and ⁷ Cancer Vaccine Development Division, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Fukuoka, and ⁸ First Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan

Purpose: The aim of this study is to find a laboratory marker for overall survival in advanced cancer patients who were vaccinated with peptides based on pre-existing, peptide-specific CTL precursors in the circulation.

Experimental Design: A group of 113 patients with advanced cancer (28 colorectal, 22 prostate, 15 lung, 14 gastric, and 34 other cancers) was enrolled in a Phase I clinical study of peptide vaccination in which peptide-specific CTL precursors of prevaccination peripheral blood mononuclear cells were measured, followed by vaccination with these peptides (maximum of four). For cellular responses, pre and postvaccination (sixth) peripheral blood mononuclear cells were provided for measurement of both peptide-specific CTL precursors by IFN- release assay and tumor reactivity by ⁵¹Cr release assay. Delayed type hypersensitivity was also measured. For humoral response, pre and postvaccination (sixth) sera were provided for measurement of peptide-reactive IgG by an ELISA.

Results: The median survival time and 1-year survival rate of the total cases were 346 ± 64.9 days and 44.6%, respectively, and those of patients vaccinated more than six times (n = 91) were 409 ± 15 days and 54.4%, respectively. In these 91 patients, the overall survival of patients whose sera showed increased levels of peptide-reactive IgG (n = 60) was significantly more prolonged (P = 0.0003) than that of patients whose sera did not (n = 31), whereas none of cellular responses correlated with overall survival.

Conclusions: Peptide-specific IgG in postvaccination sera could be a suitable laboratory maker for the prediction of prolonged survival in advanced cancer patients vaccinated with peptides based on pre-existing CTL precursors.

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