Schultz N, Oratz R, Chen D, Zeleniuch-Jacquotte A, Abeles G, Bystryn J C
Ronald O. Perelman Department of Dermatology, New York University Medical Center, New York 10016, USA.
Vaccine. 1995 Apr;13(5):503-8. doi: 10.1016/0264-410x(94)00003-6.
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.
鉴定有效的佐剂对于肿瘤疫苗的研发至关重要。为此，我们研究了一种由单磷酰脂质A（MPL）和纯化的分枝杆菌细胞壁骨架（CWS）组成的佐剂DETOX能否增强黑色素瘤疫苗的免疫原性。19例III期黑色素瘤切除患者接受了一种多价黑色素瘤抗原疫苗（40微克）与DETOX混合的免疫接种，每3周一次，共4次。7例患者接受疫苗+低剂量DETOX（10微克MPL + 100微克CWS），12例患者接受疫苗+高剂量DETOX（20微克MPL + 200微克CWS）。一个由35例患者组成的非随机对照组同样接受40微克疫苗+明矾治疗。第四次疫苗免疫后一周，接受疫苗+低剂量DETOX治疗的患者中有7/7（100%）、接受疫苗+高剂量DETOX治疗的患者中有8/12（67%）以及接受疫苗+明矾治疗的患者中有4/19（21%）的黑色素瘤抗体水平高于基线。整个DETOX组的抗体反应率为15/19（79%），而明矾组为4/19（21%）（p < 0.001）。相比之下，整个DETOX组中有50%诱导出强烈的迟发型超敏反应（DTH反应，即DTH反应比基线增加≥15毫米），明矾组为47%。整个DETOX组的无病（DF）生存期中位数为17.8个月，而明矾组为32.1个月（p < 0.05）。总之，DETOX显著增强了抗体，但对黑色素瘤疫苗免疫的DTH反应影响很小。在这项非随机研究中，与明矾相比，它似乎并未改善无病生存期。
