Soluble T-cell receptor based tumor screening reagents

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证明。该融合蛋白的TCR部分对HLA-A2背景下呈递的未突变的p53肽具有特异性。该融合蛋白已在体内模型中表征了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基于TCR或T细胞的疗法的患者，并用于评估任何给定肿瘤抗原肽作为肿瘤免疫疗法靶标的潜力。因此，将测试使用264 scTCR/IgG 1融合蛋白作为人类肿瘤的染色试剂的可行性。将使用在室载玻片上或在裸鼠中生长的人细胞系优化染色程序。融合蛋白的正常组织交叉反应性将使用正常人组织芯片来确定。最后，将使用人肿瘤组织阵列确定用264 scTCR/IgG 1染色的人肿瘤的比例。这些研究的成功完成将有助于进一步开发这种和其他基于TCR的融合蛋白用于商业化，并可能使研究人员发现其他肿瘤肽抗原，这些抗原可能是肿瘤免疫治疗的有用靶点。

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.