EFFECT OF DETOX AS AN ADJUVANT FOR MELANOMA VACCINE

The identification of effective adjuvants is critical for tumor vaccine development. Towards the end, we examined whether the immunogenicity of a melanoma vaccine could be potentiated by DETOX(TM), 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 mu g) admixed with DETOX(TM), q3 wks x 4. Seven patients received vaccine + low-dose DETOX(TM) (10 mu g MPL + 100 mu g CWS) and 12 received vaccine + high-dose DETOX(TM) (20 mu g MPL + 200 mu g CWS). A non-randomized control group of 35 patients was treated similarly with 40 mu g vaccine + alum. One week after the fourth vaccine immunization, melanoma antibodies were increased over baseline in 7/7 (100%) patients treated with vaccine + low-dose DETOX(TM), 8/12 (67%) patients treated with vaccine + high-dose DETOX, and in 4/19 (21%) of vaccine + alum patients. For the entire DETOX group, the antibody response rate was 15/19 (79%) compared 4/19 (21%) in the alum group (p<0.001). In contrast, a strong delayed-type hypersensitivity (DTH) response (greater than or equal to 15 mm increase in DTH response over baseline) was induced in 50% of the entire DETOX(TM) group versus in 47% of the alum group. Median disease-free (DF) survival for the entire DETOX(TM) group was 17.8 months compared with 32.1 months in the alum group (p<0.05). In conclusion, DETOX(TM) 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 in this non-randomized study.