ACTIVE SPECIFIC IMMUNOTHERAPY IN PATIENTS WITH MELANOMA - A CLINICAL-TRIAL WITH MOUSE ANTIIDIOTYPIC MONOCLONAL-ANTIBODIES ELICITED WITH SYNGENEIC ANTI-HIGH-MOLECULAR-WEIGHT-MELANOMA-ASSOCIATED ANTIGEN MONOCLONAL-ANTIBODIES
ACTIVE SPECIFIC IMMUNOTHERAPY IN PATIENTS WITH MELANOMA - A CLINICAL-TRIAL WITH MOUSE ANTIIDIOTYPIC MONOCLONAL-ANTIBODIES ELICITED WITH SYNGENEIC ANTI-HIGH-MOLECULAR-WEIGHT-MELANOMA-ASSOCIATED ANTIGEN MONOCLONAL-ANTIBODIES
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DOI：
10.1172/jci114952
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发表时间：
1990-12-01
影响因子：
15.9
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
在两项临床试验中，在第0天、第7天和第28天，将具有人类高分子量黑色素瘤相关抗原（hw - maa）内部图像的小鼠抗独特型单克隆抗体（MAb） MF11-30无佐剂地皮下给药给IV期恶性黑色素瘤患者。如果没有发现抗独特型抗体或其滴度降低，则进行额外注射。在第一阶段I期试验中，16名患者的初始剂量为每次注射0.5 mg，并逐渐增加到每次注射4 mg。尽管产生了抗小鼠Ig抗体，但未观察到毒性和过敏反应。在3例患者中观察到轻微反应。在第二项临床试验中，21名患者以每次注射2mg的剂量服用MAb MF11-30，因为该剂量在最初的研究中已被证明可有效诱导抗独特型抗体。2例患者无法评估；其余19例患者的平均治疗时间为34周。在这项试验中，也没有观察到毒性和过敏反应。19例免疫患者中有17例抗小鼠Ig抗体水平升高，16例产生抑制抗独特型单抗MF11-30与免疫抗hmw - maa单抗225.28结合的抗体。一名患者抗hmw - maa抗体水平升高。一名患者在持续95周的时间内，腹部多个淋巴结消失，完全缓解。在3例患者中观察到轻微反应。这些结果表明，携带HMW-MAA内部图像的小鼠抗独特型单抗可能是对黑色素瘤患者实施主动特异性免疫治疗的有用试剂。
In two clinical trials the mouse antiidiotypic monoclonal antibody (MAb) MF11-30, which bears the internal image of human high-molecular-weight-melanoma-associated antigen (HMW-MAA) was administered by subcutaneous route without adjuvants to patients with stage IV malignant melanoma on day 0, 7, and 28. Additional injections were administered if anti-antiidiotypic antibodies were not found or their titer decreased. In the first phase I trial with 16 patients the initial dose was 0.5 mg per injection and escalated to 4 mg per injection. Neither toxicity nor allergic reactions were observed despite the development of anti-mouse Ig antibodies. Minor responses were observed in three patients. In a second clinical trial MAb MF11-30 was administered to 21 patients at a dose of 2 mg per injection, since this dose had been shown in the initial study to be effective in inducing anti-antiidiotypic antibodies. Two patients were inevaluable; in the remaining 19 patients, the average duration of treatment was 34 wk. In this trial as well, neither toxicity nor allergic reactions were observed. 17 of the 19 immunized patients increased the levels of anti-mouse Ig antibodies and 16 developed antibodies that inhibit the binding of antiidiotypic MAb MF11-30 to the immunizing anti-HMW-MAA MAb 225.28. One patient increased the level of anti-HMW-MAA antibodies. One patient achieved a complete remission with disappearance of multiple abdominal lymph nodes for a duration of 95 wk. Minor responses were observed in three patients. These results suggest that mouse antiidiotypic MAb that bear the internal image of HMW-MAA may be useful reagents to implement active specific immunotherapy in patients with melanoma.