ANTI-IDIOTYPE VACCINE FOR BREAST CANCER

乳腺癌的发病率是女性死亡的常见原因， 稳定增加，复发性疾病患者的 预后 该项目旨在开发一种新的治疗方法， 涉及使用单克隆抗独特型（Id）抗体的乳腺癌 作为抗原替代物诱导抗肿瘤反应。 我们最近 产生并表征单克隆抗Id抗体，称为1D 10， 其在生物学上和抗原性上模拟一种独特和特异的表位 高分子量人乳脂肪球（HMFG）主要在高表达， 密度由人类乳腺癌和其他一些肿瘤细胞。 该表位 由命名为MC-10或BrE 1的mAb鉴定。 MC-10被用作 产生抗Id或Ab 2的免疫抗体或Ab 1。 的 由mAbMC-10（Ab 1）定义的抗原决定簇，由 11 D10或Ab 2在少数正常成人组织上最低限度地表达， 免疫过氧化物酶染色，并且在造血细胞上不存在，包括 通过流式细胞术分析检测粒细胞和血小板。 Ab 2、11 D10或抗- 用Id诱导小鼠、家兔和 猴子 此外，与HMFG Ag结合的单克隆抗-抗Ids或Ab 3具有 从用11 D10免疫的小鼠获得。 本文提出的研究将 使用明矾沉淀的抗Id 11 D10主动免疫MC患者， 1-在第1-2年期间，在1b期临床试验中，乳腺癌呈阳性。 本研究的目的是：1）确定单一 用明矾沉淀的单克隆抗Id抗体，对体液和细胞 2）确定患者产生Ab 3（Ab 1 '）的能力 免疫应答和对自体和/或 同种异体肿瘤细胞; 3）测定总体抗鼠抗体 对抗独特型抗体的反应; 4）确定最佳的 抗OId抗体的免疫调节剂量;和5）监测临床 应答 这些研究将有助于确定 最佳免疫接种和选择可能受益于抗- 独特型疫苗疗法 在1b期试验完成后，我们计划开始II期试验 在第2-3年使用最佳免疫调节剂量。 在第4年，我们将启动一项1 lb期临床试验， 抗Id 11 K10-细胞因子融合蛋白在研究中开发和测试 项目（RP）二.

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.