DENDRITIC CELL BASED VACCINATION FOR PROSTATE CANCER

描述：(申请人摘要)：前列腺癌是 男性最常见的恶性肿瘤。在播散性疾病患者中， 激素难治性疾病，治疗姑息不延长 生死存亡。申请者建议开发和评估一个 树突状细胞在前列腺癌免疫治疗中的应用 前列腺酸性磷酸酶(PAP)冲击的细胞(DC)，井 以前列腺癌抗原为特征。DC是非常有效的抗原 呈递细胞，能够使初始T淋巴细胞对蛋白质敏感 抗原，并在体外和体内激发有效的免疫反应。 申请人已经开发出从人身上获得DC的方法 并证明这些细胞，而不是单核细胞， 在体外可以使幼稚的CD4+和CD8+T细胞对标称抗原敏感。 最近，申请者小组在四名患者中展示了 肿瘤抗原注射治疗晚期恶性B细胞淋巴瘤 脉冲DC耐受性好，可诱导抗原特异性T细胞反应 和(2例)肿瘤消退。在建议的研究中， 将在体外分析PAP冲击的人树突状细胞的免疫原性， PAP冲击的大鼠DC Will的免疫原性、毒性及抗肿瘤作用 在体内对接种了Dunning肿瘤株的大鼠进行分析，以及 PAP冲击的DC的免疫原性和毒性将在 播散性前列腺癌患者。结果是 这些研究应该表明基于DC的免疫疗法是否有 在前列腺癌治疗中的潜在作用。

DESCRIPTION: (applicant's abstract): Adenocarcinoma of the prostate is the most common malignancy in men. In patients with disseminated, hormone refractory disease, treatment is palliative and does not prolong survival. The applicant proposes to develop and evaluate an immunotherapeutic approach to prostate cancer that utilizes dendritic cells (DC) pulsed with prostate acid phosphatase (PAP), a well characterized prostate antigen. DC are extremely potent antigen presenting cells, capable of sensitizing naive T lymphocytes to protein antigens and eliciting potent immune responses, in vitro and in vivo. The applicant has developed methods for obtaining DC from human peripheral blood and demonstrated that these cells, but not monocytes, can sensitize naive CD4+ and CD8+ T cells to nominal antigens, in vitro. Recently, the applicant's group has demonstrated in four patients with advanced malignant B cell lymphoma that administration of tumor antigen pulsed DC is well tolerated, induces antigen-specific T cell responses and (in two patients) tumor regression. In the proposed studies the immunogenicity of PAP pulsed human DC will be analyzed in vitro, the immunogenicity, toxicity and anti-tumor effects of PAP pulsed rat DC will be analyzed, in vivo, in rats inoculated with the Dunning tumor line, and the immunogenicity and toxicity of PAP pulsed DC will be analyzed in patients with disseminated carcinoma of the prostate. The results of these studies should indicate whether DC based immunotherapy has a potential role in the treatment of prostatic cancer.