CTL-Tumor Cell Interaction: The Generation of Molecular Probes Capable of Monitoring the HLA-A*0201-HER-2/neu Peptide Complex
Annual summary rept. 27 Feb 2004-26 Feb 2007
ROSWELL PARK CANCER INST BUFFALO NY
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The overall goal of this project is to probe the CTL - tumor cell interaction by generating scFv probes that are able to recognize the HLA-A0201-HER-2neu369-377 peptide complex. In the second 12-month funding period Feb 2005 - Feb 2006 scFv 2.3.5-58-53 was isolated following site-directed mutagenesis in the VL CDR3 and VL CDR1 of HLA-A0201 HER 2neu369-377 complex-specific scFv 2.3.5. In the 12-month period covered by this report Feb 2006 - Feb 2007, I aimed to further improve the recognition of HLA-A0201-HER-2neu369-377 complexes by scFv 2.3.5-58-53. To this end an scFv-Fc construct was utilized in an attempt to improve the avidity of the scFv for HLA-A0201 HER-2neu369-377 complexes expressed on tumor cells. Although scFv 2.3.5-58-53-Fc demonstrated modestly enhanced reactivity with HER-2neu369-377 peptide-pulsed T2 cells when compared with scFv 2.3.5-58-53 it did not exhibit enhanced reactivity with HLA-A2HER-2neu tumor cells PCA-30 and MDA-MB-231. We are actively investigating several possibilities that may account for this discrepancy.
- Medicine and Medical Research