Murine acute myeloid leukemia cells expressing the cytosine deaminase gene induce protective immunity to parental leukemic cells

by Thompson, Bridget

Despite advances in the treatment of AML, long term survival remains poor. Immunotherapy, hed at eradicating the minimal residual disease leukemic cells that lead to relapse may improve survival. We have investigated the potential utility of an AMI, vaccine expressing cytosine deaminase (CD). The expression of CD renders cells selectively sensitive to a drug, Ifluorocytosine (WC), that has no effect on normal mammaiian cells. We have generated a CD expressing variant of the murine C1498 AMI, ce11 the. We determined that in our model, in vivo 5-FC treatment does not eliminate 100% of the CD-expressing cells. Nevertheless, enhanced survival was seen with CDexpression alone and immunogenicity of the CD protein can elicit an immune reaction against parental cells by epitope spreading. Cl498 clearance was determined to be mediated mainly by CDû+ T cells. Most importantly, resistance to parental rechallenge and concurrent challenge was seen with mice irnrnunized with CD-expressing cells.