ANTI-IDIOTYPE VACCINE FOR BREAST CANCER

乳腺癌抗独特型疫苗

• 批准号: 6237506
• 负责人: MALAYA B CHATTERJEE
• 金额: $ 16.16万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-24 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6237506
• 关键词: antiidiotype antibody; antitumor antibody; breast neoplasms; cellular immunity; chimeric proteins; clinical trials; cooperative study; cytokine; cytotoxic T lymphocyte; dosage; enzyme linked immunosorbent assay; human subject; human therapy evaluation; humoral immunity; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; radioimmunoassay; tissue /cell culture

The incidence of breast cancer, a common cause of death in women, is steadily increasing and patients with recurrent disease have a poor prognosis. This project proposes to develop a new therapeutic approach to breast cancer involving the use of monoclonal anti-idiotype (Id) antibodies as antigen substitutes to induce to anti-tumor response. We have recently generated and characterized a monoclonal anti-Id antibody, termed 1D10, which mimics biologically and antigenically a distinct and specific epitope of the high MW human milk fat globule (HMFG) primarily expressed at high density by human breast cancer and some other tumor cells. This epitope is identified by the mAb designated MC-10 or BrE1. MC-10 was used as the immunizing antibody or Ab1 to which anti-ld or Ab2 was generated. The antigenic determinant as defined by the mAbMC-10 (Ab1) and represented by 11D10 or Ab2 is minimally expressed on few normal adult tissues by immunoperoxidase staining and is absent on hematopoietic cells including granulocytes and platelets by flow cytometry analysis. Ab2, 11D10 or anti- Id was used to induce tumor specific antibodies in mice, rabbits and monkeys. Also, monoclonal anti-anti Ids or Ab3 which bind to HMFG Ag have been obtained from mice immunized with 11D10. Studies proposed here will use alum precipitated anti-Id 11D10 to actively immunize patients with MC- 1- positive breast cancer in a phase 1b clinical trial during year 1-2. The objectives of this study are 1) to determine the effects of a single monoclonal anti-Id antibody precipitated with alum, on humoral and cellular immunity; 2) to determine the ability of patients to generate Ab3 (Ab1') response and cytolytic T lymphocytes (CTL) specific for autologous and/or allogeneic tumor cells; 3) to determine the overall anti-murine antibody response to the anti-idiotype antibody; 4) to determine the optimal immunomodulatory dose of the anti0Id antibody; and 5) to monitor clinical responses. These studies will assist in identification of the criteria for optimal immunization and selection of patients who may benefit from anti- idiotype vaccine therapy. At the completion of the Phase 1b trial, we plan to begin a Phase II trial in year 2-3 using the optimum immunomodulatory dose. In year 4 we will initiate a Phase 1lb clinical trial with the selected anti-Id 11K10-cytokine fusion protein developed and tested in Research Project (RP) II.

乳腺癌的发生率是女性的常见原因，是 稳定增加，复发性疾病的患者较差 预后。 该项目建议开发一种新的治疗方法 乳腺癌涉及使用单克隆抗IDiotype（ID）抗体 作为抗原替代品诱导抗肿瘤反应。 我们最近有 产生并表征单克隆抗ID抗体，称为1d10， 在生物学和抗原上模仿一个独特的特异性表位 高MW的人牛奶脂肪球（HMFG）的主要表达 人类乳腺癌和其他一些肿瘤细胞的密度。 这个表位是 由MAB指定的MC-10或BRE1识别。 MC-10用作 对产生抗LD或AB2的抗体或AB1进行免疫。 这 由MABMC-10（AB1）定义的抗原决定因素，由 11D10或AB2在很少的正常成人组织上通过 免疫过氧化物酶染色，造血细胞不存在 通过流式细胞仪分析，粒细胞和血小板。 AB2，11d10或抗 ID用于诱导小鼠，兔子和 猴子。 另外，与HMFG Ag结合的单克隆抗ANTI ID或AB3具有 从用11d10免疫的小鼠获得。 这里提出的研究将 使用明矾沉淀的抗ID 11D10积极免疫MC-患者 1-在1 - 2年期间1B期临床试验中阳性乳腺癌。 这项研究的目标是1）确定一个单一的影响 单克隆抗ID抗体与明矾沉淀，在体液和细胞上 免疫; 2）确定患者产生AB3（AB1'）的能力 针对自体和/或特异的反应和细胞溶解淋巴细胞（CTL） 同种异体肿瘤细胞； 3）确定总体抗杀菌抗体 对抗IDiotype抗体的反应； 4）确定最佳 抗0ID抗体的免疫调节剂量； 5）监测临床 回答。 这些研究将有助于确定 最佳免疫和可能受益的患者的选择 白痴型疫苗疗法。 1B期试验完成时，我们计划开始进行II期试验 在2 - 3年内，使用最佳免疫调节剂量。 在第4年 在研究中开发和测试的抗ID 11K10-循环融合蛋白 项目（RP）II。