Research Project
3493497
Many cancer cells are immunogenic, but somehow fail to stimulate the immune system. Transfecting tumor cells with allogeneic MHC class I genes stimulates the immune system to both the alloantigen and the tumor specific antigen on the tumor cells, such that the immune system can destroy parental, nontransfected tumor cells. Thus, tumor allogenization represents an approach to tumor immunotherapy whereby the host immune system may be stimulated to break tolerance against the tumor. An engineered class I gene called DC was constructed by engineering 2 cysteines into the alpha 1 domain of the Kb gene, making it appear more stable and immunogenic. DC-transfected tumor cells can stimulate long- term, systemic immunity against nontransfected tumor cells. DC is allogeneic in C57BL/6 mice from which it was derived, indicating that it will be allogeneic in all strains of mice and is capable of allogenizing all tumors from all strains of mice. Thus, in a clinical situation, DC can be a single off the shelf reagent for the allogenization of tumor cells and immunotherapy of tumors. We propose to define the conditions for maximum immunological expression of DC and endogenous class I for use in tumor immunotherapy.
