HUMAN HIGH-MOLECULAR-WEIGHT MELANOMA-ASSOCIATED ANTIGEN (HMW-MAA) MIMICRY BY MOUSE ANTIIDIOTYPIC MONOCLONAL-ANTIBODY MK2-23 - INDUCTION OF HUMORAL ANTI-HMW-MAA IMMUNITY AND PROLONGATION OF SURVIVAL IN PATIENTS WITH STAGE-IV MELANOMA
HUMAN HIGH-MOLECULAR-WEIGHT MELANOMA-ASSOCIATED ANTIGEN (HMW-MAA) MIMICRY BY MOUSE ANTIIDIOTYPIC MONOCLONAL-ANTIBODY MK2-23 - INDUCTION OF HUMORAL ANTI-HMW-MAA IMMUNITY AND PROLONGATION OF SURVIVAL IN PATIENTS WITH STAGE-IV MELANOMA
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DOI：
10.1073/pnas.89.2.466
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发表时间：
1992-01-15
影响因子：
11.1
通讯作者：
FERRONE, S
中科院分区：
文献类型：
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作者：
MITTELMAN, A;CHEN, ZJ;FERRONE, S
用小鼠抗独特型单克隆抗体（mAb） MK2-23（每次注射2 mg）免疫25例IV期黑色素瘤患者，该抗体具有抗hmw - maa mAb 763.74定义的决定因子的内部图像。2例患者无法评估，因为他们没有完成4周的治疗。只有14例患者的抗体通过血清学和免疫化学检测显示与抗hmw - maa mAb 763.74识别相同或空间接近的决定因素，并在其抗原结合位点表达mAb MK2-23定义的独特型。可能由免疫原中的卡介苗芽孢杆菌引起的副作用包括注射部位的红斑、硬结和溃疡。偶尔，患者会出现流感样症状、关节痛和肌痛。三名产生抗hmw - maa抗体的患者取得了部分反应。它包括转移灶大小的减少，1例患者持续52周，另外2例患者持续93周。14例出现抗hmw - maa抗体的患者的生存期明显（P = 0.0003）长于9例未出现体液性抗hmw - maa免疫的患者。在多变量分析中，在调整了表现状态差异后，抗hw - maa抗体的产生与生存延长之间的相关性仍然显著（P = 0.001），这是唯一发现与生存显著相关的混杂因素。最后，通过似然比检验发现抗hmw - maa抗体与患者工作状态之间存在显著的相互作用（P = 0.03），因为在工作状态低于或等于70%的患者中，抗hmw - maa抗体与生存期延长的关系比工作状态高于70%的患者更为明显。这些结果表明，抗独特型单抗MK2-23可能是一种有用的免疫原，可以在黑色素瘤患者中实施主动特异性免疫治疗。
Twenty-five patients with stage IV melanoma were immunized with the mouse anti-idiotypic monoclonal antibody (mAb) MK2-23 (2 mg per injection), which bears the internal image of the determinant defined by anti-HMW-MAA mAb 763.74. Two patients were inevaluable, since they did not complete 4 weeks of therapy. Only 14 patients developed antibodies that were shown by serological and immunochemical assays to recognize the same or spatially close determinant as the anti-HMW-MAA mAb 763.74 and to express the idiotope defined by mAb MK2-23 in their antigen-combining sites. Side effects that are likely to be caused by bacillus Calmette-Guerin present in the immunogen consisted of erythema, induration, and ulceration at the sites of the injections. Occasionally, patients complained of flu-like symptoms, arthralgias, and myalgias. Three of the patients who developed anti-HMW-MAA antibodies achieved a partial response. It consisted of a decrease in the size of metastatic lesions and lasted 52 weeks in 1 patient and 93 weeks in the other 2 patients. Survival of the 14 patients who developed anti-HMW-MAA antibodies was significantly (P = 0.0003) longer than that of the 9 patients without detectable humoral anti-HMW-MAA immunity development. In the multivariate analysis, such an association between development of anti-HMW-MAA antibodies and survival prolongation was still significant (P = 0.001) after adjustment for difference in performance status, the only confounding factor found to be significantly related to survival. Lastly, a significant (P = 0.03 by likelihood ratio test) interaction between anti-HMW-MAA antibodies and patients' performance status was found, since the prolongation of survival associated with anti-HMW-MAA antibodies was more marked in patients with a performance status of less-than-or-equal-to 70% than in those with a higher one. These results suggest that anti-idiotypic mAb MK2-23 may represent a useful immunogen to implement active specific immunotherapy in patients with melanoma.