Effect of DETOX as an adjuvant for melanoma vaccine.
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.
Schultz
N
N
Ronald O. Perelman Department of Dermatology, New York University Medical Center, New York 10016, USA.
Oratz
R
R
Chen
D
D
Zeleniuch-Jacquotte
A
A
Abeles
G
G
Bystryn
J C
JC
D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000534:Alum Compounds / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000097:blood; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000627:therapeutic use; D017358:Cell Wall Skeleton / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed; D008050:Lipid A / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology* / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D017358:Cell Wall Skeleton; D008050:Lipid A; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; C041524:aluminum sulfate; C048436:monophosphoryl lipid A