C35: A Target for Bladder and Breast Cancer Therapy

C35：膀胱癌和乳腺癌治疗的靶点

• 批准号: 6404535
• 负责人: MELINDA A BORRELLO
• 金额: $ 47.26万
• 依托单位: VACCINEX, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6404535
• 关键词: MHC class I antigen; MHC class II antigen; SCID mouse; biological signal transduction; bladder neoplasm; cell line; cytotoxic T lymphocyte; enzyme linked immunosorbent assay; gene expression; helper T lymphocyte; human tissue; immune tolerance /unresponsiveness; immunocytochemistry; immunogenetics; monoclonal antibody; neoplasm /cancer genetics; neoplasm /cancer immunology; neoplasm /cancer vaccine; tumor antigens; urinary bladder epithelium; vaccine development; xenotransplantation

DESCRIPTION (provided by applicant):The Phase I study of genes overexpressed in bladder tumors compared to normal tissue has yielded several candidates, of which the most promising is the novel gene product, C35. This gene product is overexpressed in 30 percent of primary bladder tumors as well as 70 percent of primary human breast tumors. Human CD8+ cytotoxic T lymphocytes can be induced that lyse both bladder and breast tumor cells that overexpress C35, but that do not lyse normal C35 negative cells. This indicates that immune tolerance to overexpressed C35 will probably not be an obstacle to vaccination for cancer therapy. A C35-specific monoclonal antibody has been generated and used to determine that C35 is a surface membrane protein that appears to transduce a negative growth signal to the tumor following crosslinking by purified monoclonal antibody. Pre-clinical evaluation of therapeutic applications of C35 vaccines and specific antibody are facilitated by the identification of a murine homologue of C35 that is also overexpressed in some murine tumors. The human C35 specific 2C3 monoclonal antibody is also crossreactive with murine C35 and can, therefore, be tested for clinical benefit alone or in conjunction with vaccination or chemotherapy in this animal model. PROPOSED COMMERCIAL APPLICATIONS: This research is directed at developing diagnostics and vaccines specific for bladder and breast cancer.

描述（申请人提供）：过表达基因的I期研究 与正常组织相比，膀胱肿瘤产生了几种候选者， 其中最有前途的是新型基因产物C35。该基因产物是 在 30% 的原发性膀胱肿瘤以及 70% 的膀胱肿瘤中过度表达 原发性人类乳腺肿瘤。可诱导人CD8+细胞毒性T淋巴细胞 裂解过度表达 C35 的膀胱和乳腺肿瘤细胞，但确实如此 不裂解正常 C35 阴性细胞。这表明免疫耐受 过度表达的 C35 可能不会成为癌症疫苗接种的障碍 治疗。 C35 特异性单克隆抗体已生成并用于 确定 C35 是一种表面膜蛋白，似乎可以转导 纯化后交联后向肿瘤发出负生长信号 单克隆抗体。 C35 治疗应用的临床前评估 疫苗和特异性抗体的鉴定有利于疫苗和特异性抗体的开发 C35 的鼠同源物在某些鼠肿瘤中也过度表达。这 人 C35 特异性 2C3 单克隆抗体也与鼠类发生交叉反应 因此，可以单独或联合测试 C35 的临床益处 在该动物模型中进行疫苗接种或化疗。 拟议的商业应用： 这项研究旨在开发针对膀胱的诊断方法和疫苗 和乳腺癌。