Clinical and immune responses in advanced melanoma patients immunized with an anti-idiotype antibody mimicking disialoganglioside GD2.
Clinical and immune responses in advanced melanoma patients immunized with an anti-idiotype antibody mimicking disialoganglioside GD2.
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DOI：
10.1200/jco.2000.18.2.376
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发表时间：
2000
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通讯作者：
K. Foon;J. Lutzky;R. Baral;J. Yannelli;L. Hutchins;A. Teitelbaum;O. Kashala;Ruma Das;Juanita Garrison;R. Reisfeld;M. Bhattacharya‐Chatterjee
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作者：
K. Foon;J. Lutzky;R. Baral;J. Yannelli;L. Hutchins;A. Teitelbaum;O. Kashala;Ruma Das;Juanita Garrison;R. Reisfeld;M. Bhattacharya‐Chatterjee
为了确定抗独特型疫苗的免疫应答和毒性，以及临床应答和存活率，我们启动了一项用模拟二唾液酸神经节苷脂GD 2的抗独特型抗体（TriGem）治疗晚期黑色素瘤患者的临床试验。患者和方法47名晚期黑色素瘤患者每周皮下接受1、2、4或8 mg剂量的TriGem（Titan Pharmaceuticals Inc，South San弗朗西斯科，CA）与QS-21佐剂（Aquila Biopharmaceuticals，Inc，Worcester，MA）100 μ g混合，持续4周，然后每月一次，直至疾病进展。中位年龄为57岁，有32名男性和15名女性，43%的患者接受过转移性疾病的既往治疗，55%的疾病局限于软组织，45%有内脏转移。结果47例患者中有40例患者的超免疫血清显示抗-抗-独特型（Ab 3）反应。患者Ab 3是真正的Ab 1 '，因为它特异性结合纯化的二唾液酸神经节苷脂GD 2。Ab 3抗体的同种型特异性主要由免疫球蛋白（IG）G组成，并且代表了所有IgG亚类。1例患者在24个月时持续完全缓解，12例患者在14+至37+个月（中位数，18+个月）期间稳定。32例患者在研究1 - 17个月（中位数，5.5个月）发生疾病进展，21例患者在1 - 16个月（中位数，6个月）死亡。尚未达到Kaplan-Meier推导的总中位生存期。26例仅软组织疾病患者的中位生存期尚未达到，21例内脏转移患者的中位生存期为13个月。毒性反应包括注射部位的局部反应、轻度发热和寒战。结论TriGem具有较低的毒性，能产生较强的特异性IgG免疫应答。客观反应很小，但可能对疾病进展和生存率有有利影响，这需要前瞻性随机试验。
PURPOSE To determine immune responses and toxicity to the anti-idiotype vaccine, as well as clinical responses and survival, we initiated a clinical trial for patients with advanced melanoma treated with an anti-idiotype antibody (TriGem) that mimics the disialoganglioside GD2. PATIENTS AND METHODS Forty-seven patients with advanced melanoma received either 1-, 2-, 4-, or 8-mg doses of TriGem (Titan Pharmaceuticals Inc, South San Francisco, CA) mixed with QS-21 adjuvant (Aquila Biopharmaceuticals, Inc, Worcester, MA) 100 microg subcutaneously weekly for 4 weeks and then monthly until disease progression. Median age was 57 years, there were 32 men and 15 women, 43% of patients had undergone prior therapy for metastatic disease, 55% had disease confined to soft tissue, and 45% had visceral metastasis. RESULTS Hyperimmune sera from 40 of 47 patients showed an anti-anti-idiotype (Ab3) response. Patient Ab3 was truly Ab1' because it specifically bound purified disialoganglioside GD2. The isotypic specificity of the Ab3 antibody consisted of predominantly immunoglobulin (Ig)G, and all IgG subclasses were represented. One patient had a complete response that persisted at 24 months, and 12 patients were stable from 14+ to 37+ months (median, 18+ months). Disease progression occurred in 32 patients on study from 1 to 17 months (median, 5.5 months), and 21 have died at 1 to 16 months (median, 6 months). The Kaplan-Meier-derived overall median survival has not been reached. Median survival has not been reached for the 26 patients with soft tissue disease only and was 13 months for 21 patients with visceral metastasis. Toxicity consisted of local reaction at the site of injection and mild fever and chills. CONCLUSION TriGem has minimal toxicity and generates robust and specific IgG immune responses against GD2. Objective responses were minimal, but there may be a favorable impact on disease progression and survival that will require prospective randomized trials.