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

Abstract

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 peptidespecific 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 51 Cr 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.

A Phase I-II Study of α-Galactosylceramide-Pulsed IL-2/GM-CSF-Cultured Peripheral Blood Mononuclear Cells in Patients with Advanced and Recurrent Non-Small Cell Lung Cancer

“…At present, a correlation between the induction of immune responses during various immunotherapy and the clinical outcome of treated patients remains controversial (35)(36)(37)(38). This dispute could be due to the variation of the quality of immunological assays among investigators, variable levels of tumor burden, and the different criteria used for measuring clinical responses by tumor immunotherapy.…”

Vaccination of advanced prostate cancer patients with PSCA and PSA peptide‐loaded dendritic cells induces DTH responses that correlate with superior overall survival

“…35 Other studies reported positive influences on PSA kinetics in patients receiving PSA RNA-transfected DC 7 or tumor lysate-pulsed DC. 27 In an earlier study, objective clinical remissions were observed after vaccination with DC loaded with HLA-A2-restricted PSMA-derived peptide-even in HLA-A2 negative patients.…”

A phase II study of a personalized peptide vaccination for chemotherapy-resistant advanced pancreatic cancer patients

“…With regard to post-vaccination biomarkers, several factors, including CTL responses, Th1 responses, delayed-type hypersensitivity (DTH) and autoimmunity, have been reported to be associated with clinical responses in some clinical trials (14,15). We have also shown that an increase in peptide-specific IgG and/or CTL responses after PPV is significantly associated with longer OS (11,12). In contrast to such post-vaccination biomarkers, there are currently no validated pre-vaccination prognostic biomarkers widely used.…”