Induction of immune responses and clinical efficacy in a phase II trial of IDM-2101, a 10-epitope cytotoxic T-lymphocyte vaccine, in metastatic non-small-cell lung cancer
Induction of immune responses and clinical efficacy in a phase II trial of IDM-2101, a 10-epitope cytotoxic T-lymphocyte vaccine, in metastatic non-small-cell lung cancer
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DOI：
10.1200/jco.2008.16.6462
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发表时间：
2008-09-20
影响因子：
45.3
通讯作者：
Nemunaitis, John J.
中科院分区：
文献类型：
--
作者：
Barve, Minal;Bender, James;Nemunaitis, John J.
目的产生针对多种表位和肿瘤相关抗原（TAAs）的广泛的细胞毒性T淋巴细胞应答，可能为癌症患者提供有效的免疫治疗。我们评估了由9个HLA-A2超型结合表位（两个天然表位和7个经修饰以用于最佳HLA结合或T细胞受体刺激的模拟表位）组成的单瓶肽疫苗，所述肽疫苗覆盖5个TAA和通用辅助pan-DR表位，所述肽疫苗与不完全弗氏佐剂（Montanide伊萨51; Seppic SA，巴黎，法国）一起配制成稳定乳液。IDM-2101的临床疗效，安全性和多表位免疫原性在IIIB期或IV期非小细胞肺癌（NSCLC）患者中进行了评估。患者和MethodsA共63例患者入组谁是HLA-A2阳性。终点包括生存期、安全性和免疫应答。IDM-2101（以前称为EP-2101）在前15周内每3周一次给药，然后在第1年内每2个月一次，然后在第2年内每季度一次给药，共13剂。表位特异性细胞毒性和辅助性T淋巴细胞免疫原性反应进行了测量的干扰素γ酶联免疫吸附斑点assay.ResultsNo显着的不良事件。注射部位轻度红斑和疼痛是最常见的不良反应。治疗患者的一年生存率为60%，中位生存期为17.3个月。确定了1例完全缓解和1例部分缓解。对表位肽有免疫应答的患者生存期较长（P <0.001）。结论IDM-2101耐受性良好，并有疗效证据。
PurposeGeneration of broad cytotoxic T-lymphocyte responses against multiple epitopes and tumor-associated antigens (TAAs) may provide effective immunotherapy in patients with cancer. We evaluated a single-vial peptide vaccine consisting of nine HLA-A2 supertype-binding epitopes (two native and seven analog epitopes modified for optimal HLA binding or T-cell receptor stimulation) covering five TAAs and the universal helper pan-DR epitope, formulated as a stable emulsion with incomplete Freund's adjuvant (Montanide ISA 51; Seppic SA, Paris, France). The clinical efficacy, safety, and multiepitope immunogenicity of IDM-2101 was evaluated in patients with stage IIIB or IV non-small-cell lung cancer (NSCLC).Patients and MethodsA total of 63 patients were enrolled who were positive for HLA-A2. End points included survival, safety, and immune response. IDM-2101 (previously EP-2101) was administered every 3 weeks for the first 15 weeks, then every 2 months through year 1, then quarterly through year 2, for a total of 13 doses. Epitope-specific cytotoxic and helper T-lymphocyte immunogenic responses were measured by the interferon gamma enzyme-linked immunosorbent spot assay.ResultsNo significant adverse events were noted. Low-grade erythema and pain at the injection site were the most common adverse effects. One-year survival in the treated patients was 60%, and median survival was 17.3 months. One complete and one partial response were identified. Survival was longer in patients demonstrating an immune response to epitope peptides ( P < .001).ConclusionIDM-2101 was well tolerated, and evidence of efficacy was suggested.