Effect of DETOX as an adjuvant for melanoma vaccine

Abstract

The identification of effective adjuvants is critical for tumor vaccine development. Towards this end, we examined whether the immunogenicity of a melanoma vaccine could be potentiated by DETOX™, an adjuvant consisting of monophosphoryl lipid A (MPL) and purified mycobacterial cell-wall skeleton (CWS). Nineteen patients with resected stage III melanoma were immunized with a polyvalent melanoma antigen vaccine (40 μg) admixed with DETOX™, q3 wks × 4. Seven patients received vaccine + low-dose DETOX™ (10 μg MPL + 100 μg CWS) and 12 received vaccine + high-dose DETOX™ (20 μg MPL + 200 μg CWS). A non-randomized control group of 35 patients was treated similarly with 40 μg vaccine + alum. One week after the fourth vaccine immunization, melanoma antibodies were increased over baseline in 77 (100%) patients treated with vaccine + low-dose DETOX™, 812 (67%) patients treated with vaccine + high-dose DETOX, and in 419 (21%) of vaccine + alum patients. For the entire DETOX group, the antibody response rate was 1519 (79%) compared 419 (21%) in the alum group (p < 0.001). In contrast, a strong delayed-type hypersensitivity (DTH) response (≥ 15 mm increase in DTH response over baseline) was induced in 50% of the entire DETOX™ group versus in 47% of the alum group. Median disease-free (DF) survival for the entire DETOX™ group was 17.8 months compared with 32.1 months in the alum group (p < 0.05). In conclusion, DETOX™ markedly potentiated antibody but had little effect on DTH responses to melanoma vaccine immunization. It did not appear to improve disease-free survival in comparison to alum in this non-randomized study.