IMMUNE RESPONSE ANALYSIS OF IL-12/B71 MELANOMA VACCINES

描述：（申请人的摘要）手术无法治愈的黑色素瘤是一种 一种毁灭性的疾病，中位生存期只有9-12个月，尽管 最好的化疗 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 这是我们对人体免疫反应的理解， 目前的干预相当有限。 因此，需要充分利用 从这种治疗的临床试验中获得的患者材料是显而易见的。 增强对宿主免疫反应的理解对于预防和治疗免疫缺陷至关重要。 未来治疗的合理设计。 申请人已承诺两项 试图增强宿主抗肿瘤免疫应答的临床试验 通过施用编码以下蛋白的重组金丝雀痘病毒， 细胞因子、人IL-12（ALVAC-hIL-12）或人共刺激分子， B7.1（ALVAC-hB 7.1），单独和组合。 在这里，她建议使用 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T细胞反应引起的， 通过评估外周血和肿瘤对这些癌症疫苗的反应， 用于溶细胞T细胞活性和细胞因子释放的浸润淋巴细胞 对已知肿瘤抗原的应答。 第二个目标是利用病人的肿瘤 和血清样品来鉴定和表征隐匿性肿瘤相关的 使用基于血清学的肿瘤抗原检测方法 鉴定（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。 细胞的表征 对先前表征的黑素瘤相关抗原的免疫应答 还将提供关键数据，以决定这些 新的疫苗策略应在随后的II期试验中继续进行。

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.