Polypeptide Vaccine In IL-2 Liposomes For Prostate Ca

IL-2 脂质体多肽疫苗治疗前列腺癌

• 批准号: 6438296
• 负责人: JEAN-CLAUDE BYSTRYN
• 金额: $ 37.47万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6438296
• 关键词: active immunization; antibody formation; biotechnology; clinical research; clinical trial phase I; cytotoxic T lymphocyte; delayed hypersensitivity; drug screening /evaluation; human subject; immunomodulators; interleukin 2; leukocyte activation /transformation; liposomes; neoplasm /cancer vaccine; patient oriented research; prostate neoplasms; prostate specific antigen; synthetic vaccines; vaccine development

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.

描述（由申请人提供）：我们的目标是开发一个有效的 前列腺癌的治疗方法这种疫苗必须刺激CD 8 + T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。满足 根据这些要求，我们计划从多个前列腺构建疫苗， 被人CD 8 + T细胞识别的癌症相关肽， 将它们封装到一种新的有效佐剂（IL-2脂质体）中。 我们的具体目标是：1）从六个方面构建前列腺癌疫苗 HLA-A* 0201限制性肽，其被人CD 8 + T细胞识别， 来源于四种（PSA、PSMA、MUC-1和CEA）前列腺癌的前列腺癌 相关抗原：全部包封在IL-2脂质体中。该疫苗将 含有作为阳性对照的免疫原性A*0201限制性流感肽。 2)检查疫苗刺激抗前列腺癌CD 8 + T细胞的能力 细胞、CTL、DTH和抗体应答。3)评估疫苗的安全性。 疫苗将被封装到IL-2脂质体使用的程序，我们 已经完善了。患有前列腺癌的患者， 局部治疗后复发，且HLA-A* 020 l阳性， 按顺序分配至4个治疗组之一，每组8名患者。每个 组将皮内免疫4剂疫苗（10 μ g，30 μ g， 100 μ g、300 μ g每种肽/免疫）在IL-2脂质体中，使用标准品 schedule.主要终点将是：a）疫苗诱导的刺激， 通过ELISPOT测量的CD 8 + T细胞与用于构建疫苗的肽的结合; 和B）通过标准标准测量的毒性。次要终点为 疫苗诱导的CTL、DTH和抗体应答。基于入组的8例患者 在每组中，试验将有80%的能力检测出 显著性水平为0.05，差异为2.5倍或更大， 群体间免疫反应的强度。较小的差异是 不太可能具有临床相关性。 这项工作的成功完成可能会为前列腺提供一种新的治疗方法 癌症具有最小的毒性，提高生活质量， 预防这种癌症的终极潜力。