Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinoma
Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinoma
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DOI：
10.1158/1078-0432.ccr-08-0126
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发表时间：
2008-05-15
影响因子：
11.5
通讯作者：
Schlom, Jeffrey
中科院分区：
文献类型：
--
作者：
Gulley, James L.;Arlen, Philip M.;Schlom, Jeffrey
目的：痘病毒载体具有被证实的安全记录，可用于合并多种转基因。先前的痘病毒疫苗临床试验表明，对自身抗原的免疫耐受可以被打破。癌胚抗原（CEA）和MUC-1在相当比例的常见实体癌中过表达。该研究的主要终点是疫苗安全性，次要终点是免疫和临床反应。实验设计：我们在此报告了一项对25名患者进行的初步研究，该研究采用由CEA和MUC-11基因组成的痘病毒疫苗方案，以及三种共刺激分子（TRICOM，由B7.1、细胞间粘附分子1和淋巴细胞功能相关抗原3组成）工程改造成牛痘（PANVAC-V）作为初级疫苗，并工程改造成鸡痘（PANVAC-F）作为加强疫苗。结果：疫苗耐受性良好。除注射部位反应外，在超过2%的循环中未见>= 2级毒性。在接受检测的16例患者中，有9例在接种疫苗后出现对MUC-1和/或CEA的免疫应答。一名透明细胞卵巢癌合并症状性腹水的患者在放射学和生化方面有持久的临床反应（18个月），一名乳腺癌患者证实大肝转移灶的大小减少了20%。结论：这种疫苗策略似乎是安全的，与CD8和CD4免疫应答相关，并已显示出临床活性的证据。该药物的进一步试验，无论是单独使用还是与免疫增强剂和其他治疗药物联合使用，都是有必要的。
Purpose: Poxviral vectors have a proven safety record and can be used to incorporate multiple transgenes. Prior clinical trials with poxviral vaccines have shown that immunologic tolerance to self-antigens can be broken. Carcinoembryonic antigen (CEA) and MUC-1 are overexpressed in a substantial proportion of common solid carcinomas. The primary end point of this study was vaccine safety, with immunologic and clinical responses as secondary end points.Experimental Design: We report here a pilot study of 25 patients treated with a poxviral vaccine regimen consisting of the genes for CEA and MUC-11, along with a triad of costimulatory molecules (TRICOM; composed of B7.1, intercellular adhesion molecule 1, and lymphocyte function - associated antigen 3) engineered into vaccinia (PANVAC-V) as a prime vaccination and into fowlpox (PANVAC-F) as a booster vaccination.Results: The vaccine was well tolerated. Apart from injection-site reaction, no grade >= 2 toxicity was seen in more than 2% of the cycles. Immune responses to MUC-1 and/or CEA were seen following vaccination in 9 of 16 patients tested. A patient with clear cell ovarian cancer and symptomatic ascites had a durable (18-month) clinical response radiographically and biochemically, and one breast cancer patient had a confirmed decrease of >20% in the size of large liver metastasis.Conclusions: This vaccine strategy seems to be safe, is associated with both CD8 and CD4 immune responses, and has shown evidence of clinical activity. Further trials with this agent, either alone or in combination with immunopotentiating and other therapeutic agents, are warranted.