ANTI-IDIOTYPE VACCINE FOR BREAST CANCER

乳腺癌是女性的常见死因，其发病率为 稳步增长和复发性疾病患者有较差的 预后。该项目建议开发一种新的治疗方法来治疗 涉及使用抗独特型(ID)单抗的乳腺癌 作为抗原替代品诱导产生抗肿瘤反应。我们最近做了 制备并鉴定了一种名为1D10的抗ID单抗， 它在生物学上和抗原性上模拟了一个独特和特定的表位 高分子量人乳脂球(HMFG)主要在高表达 人类乳腺癌和其他一些肿瘤细胞的密度。这个表位是 由指定为MC-10或Bre1的单抗鉴定。MC-10被用作 产生抗1d或ab2抗体的免疫抗体或ab1。这个 由mAbMC-10(Ab1)定义的抗原决定簇，由 11D10或AB2在少数正常成人组织中最低限度地表达 免疫过氧化物酶染色，在造血细胞上不存在，包括 用流式细胞仪分析粒细胞和血小板。AB2、11D10或抗- 用ID诱导小鼠、兔和小鼠的肿瘤特异性抗体。 猴子。此外，与hMFG抗原结合的单抗抗ID或ab3具有 从11D10免疫的小鼠身上获得。这里提出的研究将 明矾沉淀抗ID 11D10主动免疫MC-1患者 1-阳性乳腺癌在1-2年的1b期临床试验中。 这项研究的目标是1)确定单一的 明胶沉淀法、体液沉淀法和细胞沉淀法制备抗ID单抗 免疫；2)测定患者产生ab3(ab1‘)的能力 自体和/或自身特异性的反应和细胞溶解T淋巴细胞(CTL) 同种异体肿瘤细胞；3)测定总抗鼠抗体 对抗独特型抗体的反应；4)确定最佳 抗Oid抗体的免疫调节剂量；5)监测临床 回应。这些研究将有助于确定 最优免疫和选择可能受益于抗-HBs的患者 独特型疫苗疗法。 在1b阶段试验结束后，我们计划开始第二阶段试验。 在2-3年使用最佳免疫调节剂量。 在第四年，我们将启动一项1lb期临床试验， 抗ID11K10-细胞因子融合蛋白的研制与试验 项目(RP)2.

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.