Quantitation of immune responses against the cancer testis antigen NY-ESO-1 following vaccination with protein with and without ISCOMATRIX adjuvant

Abstract

2518 Background: One major challenge for cancer immunology is the measurement of the immune response so that any relationship to clinical outcomes can be evaluated using stringent criteria. Methods: We have applied a novel scoring system in order to better quantitate integrated antibody and cellular immune responses in patients vaccinated with a full-length protein cancer testis antigen, NY-ESO-1. The score accounts for rate of onset, duration and intensity of an immune response (the immune equivalent of AUC). Forty-six patients (pts), 42 with melanoma, all with fully resected disease, were vaccinated IM on three occasions at monthly intervals. NY-ESO-1 protein was administered with or without the ISCOMATRIX adjuvant, which has been shown to induce both antibody and T cell responses. NY-ESO-1 ISCOMATRIX vaccine doses were:10μg (n=3), 30μg (n=3), and 100μg (n=16). 16 pts received 100μg NY-ESO-1 protein alone and 8 pts received placebo. NY-ESO-1 immunity was assessed by Delayed Type Hypersensitivity (DTH) to NY-ESO-1 protein, by ELISA for antibody and by tetramer and ICS for the number of reactive NY-ESO-1 CD8+ & CD4+ T cells. Results: Although low level immune responses were seen against protein alone, the addition of adjuvant greatly increased immune responses in a dose-dependent fashion. In an unplanned analysis, the relapse free survival (RFS) of melanoma pts was assessed. Despite small numbers, patients in cohorts with higher immune response scores appeared to have longer RFS than those from cohorts with low scores. Conclusions: A prospective evaluation of this is required determine whether immune responses to NY-ESO-1 is correlated clinical outcome of pts with tumours which express this antigen. Using a system to quantitate immune responses will also facilitate strategies aimed at optimising vaccine potency. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CSL Ltd. CSL Ltd.