Dendritic Cell Vaccine in Metastatic Prostate Cancer

说明(由申请人提供)：不能手术、晚期的治疗方案 前列腺癌(PrCa)是有限的，免疫疗法是一种替代疗法。 允许产生大量枝晶的方法的发现 细胞(DC)引发了许多旨在诱导肿瘤特异性的临床试验 豁免权。然而，向DC递送肿瘤抗原的最佳策略 仍然是需要确定的关键参数之一。杀死的肿瘤 细胞作为肿瘤相关抗原(TAA)的来源，在DC基础上 免疫提供了一种新策略，允许同时呈现CTL和T细胞 辅助表位。这可以允许呈现多个TAA表位和 包括CD8和CD4T细胞在内的多种效应器的多样化免疫反应， NK细胞和巨噬细胞，从而增加体内肿瘤的机会 拒绝。基于我们的体外实验结果，我们认为树突状细胞负载 前列腺癌患者体内可激发前列腺癌特异性免疫 活体内的反应。我们建议对15名人类白细胞抗原A2.1携带者进行临床试验。 激素抵抗型前列腺癌将接种自体疫苗 单核细胞来源的DC负载杀伤的PrCa细胞系(LNCaP和PC3)。目标1： 树突状细胞负载灭活同种异体Prca的安全性和耐受性 细胞系。目的2：评价新城疫患者的免疫水平和临床反应 接种致死的同种异体PrCa细胞系的DC的患者。 这项研究将使我们能够确定DC的安全性和耐受性 装载了杀死的同种异体肿瘤细胞作为TAA的来源。它还将 允许我们深入了解前列腺癌诱导的免疫水平 由DC提供。

DESCRIPTION (Provided by applicant): Treatment options for inoperable, advanced prostate cancer (PrCa) are limited and immunotherapy represents an alternative. The discovery of methods allowing generation of large numbers of dendritic cells (DCs) prompted numerous clinical trials aimed at eliciting tumor specific immunity. However, the optimal strategy for tumor antigen delivery to DCs remains one of the key parameters that need yet to be determined. Killed tumor cells, as a source of tumor associated antigens (TAA), in the DC-based immunization offer a novel strategy that allows presentation of both CTL and T helper epitopes. This may permit presentation of multiple TAA epitopes and a diverse immune response with multiple effectors including CD8 and CD4 T cells, NK cells and macrophages, thus increasing the chances for in vivo tumor rejection. Based on our in vitro results we propose that Dendritic cells loaded with prostate cancer bodies can elicit prostate cancer-specific immune responses in vivo. We propose a clinical trial in 15 HLA-A2.1 patients with hormone-refractory prostate carcinoma who will be vaccinated with autologous monocyte-derived DCs loaded with killed PrCa cell lines (LnCAP and PC3). Aim 1: To determine safety and tolerability of DCs loaded with killed allogeneic PrCa cell lines. Aim 2: To evaluate the level of immune and clinical responses in patients vaccinated with DCs loaded with killed allogeneic PrCa cell lines. This study will permit us to establish the safety and tolerability of DCs loaded with killed allogeneic tumor cells as a source of TAA. It will also permit us to gain insights into the level of prostate cancer immunity induced by DCs.