Soluble T-cell receptor based tumor screening reagents

基于可溶性T细胞受体的肿瘤筛查试剂

• 批准号: 6739257
• 负责人: HING C. WONG
• 金额: $ 10万
• 依托单位: ALTOR BIOSCIENCE. LLC
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6739257
• 关键词: MHC class I antigen; T cell receptor; athymic mouse; biotechnology; cell line; chimeric proteins; flow cytometry; immunocytochemistry; molecular probes; neoplasm /cancer immunotherapy; peptide chemical synthesis; protein quantitation /detection; reagent /indicator; tumor antigens

DESCRIPTION (provided by applicant): The goal of this research is to demonstrate proof-of-principle for using a T-cell receptor (TCR)-based fusion protein as a staining reagent for human tumors. The TCR portion of this fusion protein is specific for an unmutated p53 peptide presented in the context of HLA-A2. This fusion protein has been characterized for MHC restricted peptide specific binding, Fc receptor binding, and anti-tumor activity in an in vivo model. TCR technology may be useful for screening patients who may benefit from a TCR or T-cell based therapy and for evaluating the potential of any given tumor antigen peptide as a target for tumor immunotherapy. Thus, the feasibility of using the 264scTCR/IgG1 fusion protein as a staining reagent for human tumors will be tested. The staining procedure will be optimized using human cell lines grown on chamber slides or in nude mice. Normal tissue cross-reactivity of the fusion protein will be determined using normal human tissue histoarrays. Finally, the proportion of human tumors that stain with 264scTCR/IgG1 will be determined using human tumor histoarrays. Successful completion of these studies will facilitate further development of this and other TCR based fusion proteins for commercialization and potentially allow investigators to discover other tumor peptide antigens that may be useful targets for tumor immunotherapy.

描述（由申请人提供）：本研究的目的是证明使用基于 T 细胞受体 (TCR) 的融合蛋白作为人类肿瘤染色试剂的原理验证。该融合蛋白的 TCR 部分对 HLA-A2 中存在的未突变 p53 肽具有特异性。该融合蛋白已在体内模型中表征为 MHC 限制性肽特异性结合、Fc 受体结合和抗肿瘤活性。 TCR 技术可用于筛选可能受益于 TCR 或 T 细胞治疗的患者，并可用于评估任何给定肿瘤抗原肽作为肿瘤免疫治疗靶点的潜力。因此，将测试使用264scTCR/IgG1融合蛋白作为人类肿瘤染色试剂的可行性。将使用在室载玻片或裸鼠中生长的人类细胞系来优化染色程序。将使用正常人组织组织阵列测定融合蛋白的正常组织交叉反应性。最后，将使用人类肿瘤组织阵列确定用 264scTCR/IgG1 染色的人类肿瘤的比例。这些研究的成功完成将促进该融合蛋白和其他基于 TCR 的融合蛋白的进一步开发以实现商业化，并有可能让研究人员发现其他可能成为肿瘤免疫治疗有用靶标的肿瘤肽抗原。