Targeting Mutated Epidermal Growth Factor Receptor.
Annual rept. 1 Jul 98-30 Jun 99
PENNSYLVANIA UNIV PHILADELPHIA WISTAR INST
Pagination or Media Count:
This project is aimed at developing specific and effective vaccines for immunotherapy of breast cancer targeting mutated epidermal growth factor receptor mEGF-R in a rat model. During the first 2 years of funding, vaccines of mEGF-R peptides, recombinant protein and viral vector were produced and shown to induce humoral immunity to rat mEGF-R in rats. Furthermore, rat mammary carcinoma cells were transfected with rat mEGF-R cDNA to provide target cells for in vivo vaccinations. During the past third year of funding, our efforts to isolate transfectants expressing the mutated epitope were unsuccessful, presumably due to mutations in the rat mEGF-R vector. We have evaluated breast carcinoma patients humoral and cellular immune responses to mEGF-R protein and peptides. Four of four patients tested had circulating antibodies that bound to mutated, but not normal, EGF-R protein. Neither of the 2 healthy donors sera bound to mEGF-R. The peripheral blood lymphocytes of 2 of 5 breast cancer patients significantly proliferated to stimulation with mEGF-R protein andor peptides. These data suggest that the mEGF-R epitope is immunogenic in breast cancer patients and, therefore, it should be possible to boost this immunity with mEGF-R vaccines.
- Anatomy and Physiology
- Medicine and Medical Research