IMMUNE RESPONSE ANALYSIS OF IL-12/B71 MELANOMA VACCINES

描述：(申请者摘要)无法手术治愈的黑色素瘤是一种 破坏性疾病，中位生存期只有9-12个月，尽管 最好的化疗方案。采用主动免疫疗法的最新研究 治疗黑色素瘤的方法已经开始产生令人鼓舞的结果。尽管 这就是我们对人类免疫反应的理解 目前，干预措施相当有限。因此，有必要充分利用 从这种疗法的临床试验中获得的患者材料是显而易见的。 加强对宿主免疫反应的了解对于 合理设计未来的治疗方法。申请人已经承担了两项 试图增强宿主抗肿瘤免疫反应的临床试验 通过注射重组金丝雀痘病毒编码 细胞因子，人IL-12(ALVAC-hIL-12)或人共刺激分子， B7.1(ALVAC-hB7.1)，单独及联合应用。在这里，她提议使用 在这两个免疫治疗试验中产生的患者材料 目的。首先，她将描述患者的T细胞反应。 通过评估外周血和肿瘤对这些肿瘤疫苗的反应 浸润性淋巴细胞对T细胞杀伤活性和细胞因子释放的影响 对已知的肿瘤抗原作出反应。第二个目标是使用患者肿瘤 和血清样本以识别和表征隐匿性肿瘤相关 采用基于血清学的肿瘤抗原方法的抗原 标识(Serex)。她预计这些研究将推动我们的 了解癌症和免疫系统之间的相互作用，以及 确定免疫治疗的新靶点，从而促进 改进的癌症疫苗的开发。细胞的特性 对已鉴定的黑色素瘤相关抗原的免疫反应 还将提供关键数据，以决定是否这些 在随后的第二阶段试验中应寻求新的疫苗策略。

DESCRIPTION: (Applicant's Abstract) Surgically incurable melanoma is a devastating disease with a median survival of only 9-12 months despite the best available chemotherapy. Recent studies employing active immunotherapy approaches for melanoma have begun to yield encouraging results. Despite this, our understanding of human immune response subsequent to immunological intervention is, at present quite limited. Thus the need to fully exploit patient material obtained from clinical trials of such therapy is apparent. An enhanced understanding of host immune responses is crucial to the rational design of future therapies. The applicant has undertaken two clinical trials which attempt to augment host antitumor immune responses through the administration of recombinant canary pox viruses encoding the cytokine, human IL-12 (ALVAC-hIL-12) or the human costimulatory molecule, B7.1 (ALVAC-hB7.1), separately and in combination. Here she proposes to use the patient material generated in these two immunotherapy trials for two purposes. First, she will characterize patient T cell responses elicited in response to these cancer vaccines by evaluating peripheral blood and tumor infiltrating lymphocytes for cytolytic T cell activity and cytokine release in response to known tumor antigens. A second goal is to use patient tumor and sera samples to identify and characterize cryptic tumor-associated antigens employing a serologically based method of tumor antigen identification (SEREX). She anticipates that these studies will advance our understanding of the interaction between cancer and the immune system, and identify novel targets for immunotherapy, thereby facilitating the development of improved cancer vaccines. Characterization of the cellular immune response to previously characterized melanoma-associated antigens will also provide data critical in making the decision as to whether these novel vaccine strategies should be pursued in subsequent Phase II trials.