Induction of tumour-specific immunity by manipulating the expression of major histocompatibility complex molecules on...

Class I major histocompatibility complex (MHC) molecules form part of the target structure recognized by the host cytotoxic T cells (CTL) to reject tumour cells. Many types of malignant tumour cells are reported in which expression of class I MHC genes is down-regulated. By DNA-mediated gene transfer, it is possible to re-express the 'missing' syngeneic (genetically identical) or to introduce 'new' allogeneic (genetically dissimilar) class I MHC genes into these MHC-deficient tumours. In both instances, the immunogenicity of the transfected tumour cells is greatly enhanced and results in their rejection in vivo. More importantly, these 'modified' tumour cells, which are positive for class I MHC molecules, can simultaneously generate an immunity against the 'wild-type' tumour cells which do not express these molecules. These observations suggest the distinct possibility of using gene transfer as a molecular immunotherapeutic approach to abrogate tumour growth.