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）的乳腺癌 抗体作为抗原替代物以诱导抗肿瘤应答。 我们 最近已经产生并表征了单克隆抗Id抗体， 称为11 D10，其在生物学和抗原性上模拟一种独特的， 高分子量人乳脂肪球（HMFG）的特异性表位主要 在人乳腺癌和其他肿瘤中高密度表达 细胞 该表位由命名为MC-10或BrE 1的mAb鉴定。 用MC-10作为免疫抗体或Ab 1，抗Id或Ab 2 产生了。 由mAb MC-10定义的抗原决定簇 (Ab1)并且由11 D10或Ab 2表示的是在少数上最低表达的 免疫过氧化物酶染色显示正常成人组织， 造血细胞包括粒细胞和血小板上不存在， 流式细胞术分析。 用Ab 2、11 D10或抗Id诱导肿瘤 小鼠、兔子和猴子体内的特异性抗体。 此外，单克隆抗- 已经从小鼠中获得了与HMFG Ag结合的抗Ids或Ab 3 用11 D10免疫。 这里提出的研究将使用明矾沉淀 抗Id 11 D10抗体主动免疫MC-10阳性乳腺癌患者 癌症1B期临床试验。 本研究的目的是 1)为了确定单个单克隆抗Id抗体的作用， 用明矾沉淀，对体液和细胞免疫; 2） 确定患者产生Ab 3（Ab 1 ′）应答的能力， 对自体和/或同种异体特异性的细胞溶解性T淋巴细胞（CTL） 肿瘤细胞; 3）确定总体抗鼠抗体应答 抗独特型抗体; 4）确定最佳 抗Id抗体的免疫调节剂量;和5）监测 临床反应。 这些研究将有助于确定 最佳免疫标准和选择可能 从抗独特型疫苗治疗中获益。

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 anti-tumor responses. We have recently generated and characterized a monoclonal anti-Id antibody, termed 11D10, 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-Id or Ab2 was generated. The antigenic determinant as defined by the mAb MC-10 (Ab1) and represented by 11D10 or Ab2 is minimally expressed on few normal adult tissues as demonstrated 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-10 positive breast cancer in a phase 1b clinical trial. 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 anti Id 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.