MELANOMA VACCINE--TYROSINASE/GP100 W/ MONTANIDE ISA51 OR GM CSF

黑色素瘤疫苗 - 酪氨酸酶/GP100 W/ Montanide ISA51 或 GM CSF

• 批准号: 6263712
• 负责人: VERNON K. SONDAK
• 金额: $ 0.02万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6263712
• 关键词: cellular immunity; clinical research; colony stimulating factor; combination cancer therapy; enzyme linked immunosorbent assay; enzyme therapy; glycoproteins; human subject; human therapy evaluation; immunologic skin test; melanoma; monophenol monooxygenase; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; synthetic vaccines

In this protocol, we propose to extend observations made during a previous clinical trial in which patients with resected melanoma that were immunized with a peptide vaccine demonstrated augmented T cell immunity specifically directed toward the immunizing antigen. In that trial, as in several others in which patients with melanoma were immunized with epitope peptides, incomplete Freund's adjuvant (IFA) was used and the duration of immunization schedules was brief. Important questions that remain to be resolved in the cancer vaccine field include the optimal dose, schedule and adjuvant combination for immunization. In the current trial, we will perform a two center randomized phase II trial in which HLA-A2+ patients with resected stages IIA and IIB melanoma will be vaccinated with one of three vaccine regimens. Arm A will consist of eight paired vaccinations with tyrosinase plus IFA and gp 100 plus IFA over increasing intervals of time as the "standard" regimen. Patients in Arb B will receive the some regimen as in Arm A but with a block co-polymer adjuvant CRL 1005 emusified with the peptide/IFA combination. Patients in Arm C will receive GM-CSF injected subcutaneously proximal to the vaccination site the day of and for four days after vaccination with the same regimen as Arm A. The principal endpoint of the study to be conducted as a collaboration between the University of Michigan andUSC/Norris Cancer Center will be the immu e response to the antigen peptides and a quantitative comparison of immune reaponses on each arm. Skin testing with the peptides, cytokine release by peptide stimulated CTL grown from peripheral blood, and precursor CTL frequency estimated from ELISPOT assays prior to and after vaccinations will be used to measure immune responses. Assessment of T cell receptor zeta chain expression will also be performed. The results of this trial will be used to design the experimental arm of future randomized phase III trials in patients with resected high risk melanoma. Specific GCRC support is being requested for the performance of pretreatment skin testing and plasmapheresis before and after vaccination on a total of 40 patients over two years.

在本方案中，我们建议扩展之前的临床试验中的观察结果，在该临床试验中，接受肽疫苗免疫的切除黑色素瘤的患者表现出增强的 T 细胞免疫力，专门针对免疫抗原。 在该试验中，与其他几项用表位肽对黑色素瘤患者进行免疫的试验一样，使用了不完全弗氏佐剂（IFA），并且免疫计划的持续时间很短。 癌症疫苗领域仍有待解决的重要问题包括免疫的最佳剂量、时间表和佐剂组合。 在当前的试验中，我们将进行一项两中心随机 II 期试验，其中切除 IIA 期和 IIB 期黑色素瘤的 HLA-A2+ 患者将接种三种疫苗方案中的一种。 A 组将由八对酪氨酸酶加 IFA 和 gp 100 加 IFA 疫苗组成，疫苗接种时间间隔逐渐增加，作为“标准”方案。 Arb B 中的患者将接受与 A 组中相同的治疗方案，但使用与肽/IFA 组合乳化的嵌段共聚物佐剂 CRL 1005。 C 组的患者将在接种当天和接种后四天内接受与 A 组相同的方案在疫苗接种部位附近皮下注射的 GM-CSF。该研究的主要终点将与密歇根大学合作进行USC/Norris 癌症中心将针对抗原肽进行免疫反应，并对每只手臂上的免疫反应进行定量比较。 使用肽进行皮肤测试、从外周血中生长的肽刺激的 CTL 释放细胞因子，以及在接种疫苗之前和之后通过 ELISPOT 测定估计的前体 CTL 频率，将用于测量免疫反应。 还将对 T 细胞受体 Zeta 链表达进行评估。 该试验的结果将用于设计未来针对已切除高风险黑色素瘤患者的随机 III 期试验的实验组。 两年内，总共 40 名患者在疫苗接种前后进行了治疗前皮肤测试和血浆置换，目前正在请求特定的 GCRC 支持。