Soluble T-cell receptor based tumor screening reagents

描述(由申请人提供)：这项研究的目标是证明使用基于T细胞受体(TCR)的融合蛋白作为人类肿瘤染色试剂的原理。该融合蛋白的TCR部分是针对在人类白细胞抗原A2背景下出现的未突变的p53多肽的。该融合蛋白具有MHC限制性多肽结合、Fc受体结合和体内抗肿瘤活性。TCR技术可用于筛选可能从TCR或基于T细胞的治疗中受益的患者，以及评估任何给定的肿瘤抗原肽作为肿瘤免疫治疗靶点的潜力。因此，将264scTCR/IgG1融合蛋白用作人类肿瘤染色试剂的可行性将得到检验。染色程序将使用在室内载玻片上生长的人类细胞系或在裸鼠身上进行优化。融合蛋白的正常组织交叉反应将使用正常的人体组织组织阵列来确定。最后，将使用人类肿瘤组织阵列来确定264scTCR/IgG1染色的人类肿瘤的比例。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可能成为肿瘤免疫治疗有用靶点的肿瘤多肽抗原。

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.