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 micrograms) admixed with DETOX, q3 wks x 4. Seven patients received vaccine + low-dose DETOX (10 micrograms MPL + 100 micrograms CWS) and 12 received vaccine + high-dose DETOX (20 micrograms MPL + 200 micrograms CWS). A non-randomized control group of 35 patients was treated similarly with 40 micrograms 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, 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 (> or = 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.

• Authors: N Schultz, R Oratz, D Chen, A Zeleniuch-Jacquotte, G Abeles, J C Bystryn
• Journal: Vaccine (Vaccine) Vol. 13 Issue 5 Pg. 503-8 (Apr 1995) ISSN: 0264-410X [Print] Netherlands
• PMID: 7639018 (Publication Type: Clinical Trial, Comparative Study, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Alum Compounds
• Antibodies, Neoplasm
• Antigens, Neoplasm
• Cell Wall Skeleton
• Lipid A
• Melanoma-Specific Antigens
• Neoplasm Proteins
• aluminum sulfate
• monophosphoryl lipid A

Topics

• Adjuvants, Immunologic (adverse effects, therapeutic use)
• Adult
• Aged
• Alum Compounds (therapeutic use)
• Antibodies, Neoplasm (biosynthesis, blood)
• Antigens, Neoplasm (immunology, therapeutic use)
• Cell Wall Skeleton (adverse effects, immunology, therapeutic use)
• Drug Synergism
• Female
• Humans
• Hypersensitivity, Delayed
• Lipid A (adverse effects, analogs & derivatives, immunology, therapeutic use)
• Male
• Melanoma (immunology, therapy)
• Melanoma-Specific Antigens
• Middle Aged
• Neoplasm Proteins (immunology, therapeutic use)