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. ? ?
| Zhu, Xiaoyun; Belmont, Heather J; Price-Schiavi, Shari et al. (2006) Visualization of p53(264-272)/HLA-A*0201 complexes naturally presented on tumor cell surface by a multimeric soluble single-chain T cell receptor. J Immunol 176:3223-32 |
