Polypeptide Vaccine In IL-2 Liposomes For Prostate Ca

描述(由申请人提供)：我们的目标是开发一种有效的 前列腺癌疫苗。这样的疫苗必须刺激CD8T细胞对抗 多种前列腺癌抗原；因为这更有可能杀死癌细胞 并避免肿瘤抗原表达的异质性。要让人满意 根据这些要求，我们计划构建一种多个前列腺的疫苗 人CD8 T细胞识别的肿瘤相关多肽 将它们封装成一种新颖而有效的佐剂(IL-2脂质体)。 我们的具体目标是：1)从六个方面构建前列腺癌疫苗 人CD8T细胞识别的HLA-A*020L限制性多肽 来自四种前列腺癌(PSA、PSMA、MUC-L和CEA) 相关抗原：全部被包裹到IL-2脂质体中。疫苗将会 作为阳性对照，含有免疫原性、A*0201限制性的流感多肽。 2)检测疫苗刺激抗前列腺癌CD8 T的能力 细胞、CTL、DTH和抗体反应。3)评价疫苗的安全性。 疫苗将被封装到IL-2脂质体中，使用我们的程序 已经很完美了。前列腺癌患者的生化指标 局部治疗后复发，且人类白细胞抗原A*0201阳性，会吗？ 按顺序分配到4个治疗组中的一个，每组8例。每个人 组将皮内接种4剂疫苗(10g，30ug， 100ug、300ug)在IL-2脂质体中，使用标准的 时间表。主要终点将是：a)疫苗诱导的刺激 用ELISPOT法检测构建疫苗所用的多肽对CD8T细胞的影响； 和b)以标准标准衡量的毒性。次要端点将是 疫苗诱导的CTL、DTH和抗体反应。根据输入的8名患者 进入每一组，审判将有80%的权力通过 显著水平0.05，差异2.5倍或更大 群体之间的免疫反应的大小。较小的差异是 不太可能与临床相关。 这项工作的成功完成可能会为前列腺癌提供一种新的治疗方法 毒性最小的癌症，可以提高生活质量，而且 预防这种癌症的终极潜力。

DESCRIPTION (Provided by applicant): Our goal is to develop an effective vaccine for prostate cancer. Such a vaccine must stimulate CD8+ T cells against multiple prostate cancer antigens; as this is more likely to kill cancer cells and to circumvent heterogeneity in the expression of tumor antigens. To satisfy these requirements, we plan to construct a vaccine from multiple prostate cancer-associated peptides that are recognized by human CD8+ T cells and to encapsulate them into a novel and potent adjuvant (IL-2 liposomes). Our specific aims are to: 1) Construct a prostate cancer vaccine from six HLA-A*020l restricted peptides that are recognized by human CD8+ T cells and that are derived from four (PSA, PSMA, MUC-l and CEA) prostate cancer associated antigens: all encapsulated into IL-2 liposomes. The vaccine will contain, as a positive control, an immunogenic, A*0201 restricted, flu peptide. 2) Examine the ability of the vaccine to stimulate anti-prostate cancer CD8 + T cell, CTL, DTH and antibody responses. 3) Evaluate the safety of the vaccine. The vaccine will be encapsulated into IL-2 liposomes using procedures that we have already perfected. Patients with prostate cancer who have biochemical recurrence after local therapy, and are HLA-A*020l positive, will he sequentially allocated to one of 4 treatment groups of 8 patients each. Each group will be immunized intradermally to one of 4 doses of vaccine (10g, 30ug, l00ug, 300ug of each peptide/immunization) in IL-2 liposomes, using a standard schedule. The primary end-points will be: a) Vaccine-induced stimulation of CD8+ T cells to the peptides used to construct the vaccine measured by ELISPOT; and b) toxicity measured by standard criteria. Secondary end-points will be vaccine-induced CTL, DTH and antibody responses. Based on 8 patients entered into each group, the trial will have 80 percent power to detect with a significance level of 0.05, differences of two and a half fold or greater in the magnitude of immune responses between groups. Smaller differences are unlikely to be clinically relevant. Successful completion of this work may provide a new treatment for prostate cancer that has minimal toxicity, that improves quality of life, and that has the ultimate potential to prevent this cancer.