A phase I trial of vaccination of CA9-derived peptides for HLA-A24-positive patients with cytokine-refractory metastatic renal cell carcinoma
A phase I trial of vaccination of CA9-derived peptides for HLA-A24-positive patients with cytokine-refractory metastatic renal cell carcinoma
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DOI：
10.1158/1078-0432.ccr-05-2253
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发表时间：
2006-03-15
影响因子：
11.5
通讯作者：
Itoh, K
中科院分区：
文献类型：
--
作者：
Uemura, H;Fujimoto, K;Itoh, K
目的：在患有进行性肾细胞癌难治性转移性肾细胞癌（RCC）的患者中进行I期肽疫苗接种试验，以评估三种肽的毒性和诱导免疫应答的能力（CA 9 p219 -227、p288-296和p323-331），其来源于CA 9，一种在RCC中广泛表达的肿瘤相关抗原。23例人类白细胞抗原（HLA）-A24阳性的组织学确诊的RCC患者入组。合格性包括使用白细胞介素-2和/或IFN-α进行标准细胞因子治疗后的疾病进展。患者皮下接种疫苗。以2周的间隔将三种肽乳化在不完全弗氏佐剂中。采集疫苗接种前和接种后血样，用于毒性评估和免疫学研究。患者的临床反应进行了监测，3-monthly basis.Results：疫苗接种耐受性良好，没有任何重大不良事件。大多数患者在第6次或第9次疫苗接种后产生肽特异性CTL和/或免疫球蛋白G，随后CTL频率和肽反应性血清IgG水平逐渐增加。3例多发性肺转移患者显示部分缓解，转移灶消失和缩小。此外，在6名患者中观察到疾病稳定>6个月（中位持续时间，12.2个月）。此外，所有患者的中位生存时间谁是渐进的试验招募失败后免疫治疗是21.0个月（5-35个月）。结论：这些结果表明，这些肽的疫苗接种是安全的，并建议进一步试验HLA-A24阳性转移性RCC患者。
Purpose: A phase I peptide vaccination trial was done in patients with progressive cytokine-refractory metastatic renal cell carcinoma (RCC) to assess both the toxicity and capability to induce immune responses of three peptides (CA9p219-227, p288-296, and p323-331) derived from CA9, a tumor-associated antigen ubiquitously expressed in RCC.Experimental Design: Twenty-three patients positive for human leukocyte antigen (HLA) -A24 with histologically confirmed RCC were enrolled. Eligibility included progressive disease after standard cytokine therapy with interleukin-2 and/or IFN-alpha. Patients were vaccinated s.c. with the three peptides emulsified in incomplete Freund's adjuvant at 2-week intervals. Pre- and post-vaccination blood samples were obtained for toxicity assessment and immunologic studies. Patients were monitored for clinical responses on a 3-monthly basis.Results: Vaccinations were well tolerated without any major adverse event. Most of the patients developed peptide-specific CTLs and/or immunoglobulin G reactive to the peptides after the 6th or 9th vaccination, followed by a gradual increase in both CTL frequency and levels of peptide-reactive serum IgG. Three patients with multiple lung metastases showed partial responses with disappearance and shrinking of metastatic lesions. Additionally, stable disease for >6 months was observed in six patients (median duration, 12.2 months). Moreover, the median survival time of all patients who were progressive at trial enrollment after failing immunotherapy was 21.0 months (5-35 months).Conclusions: These results suggest that vaccination of these peptides is safe and recommended for further trials for HLA-A24-positive metastatic RCC patients.