Immunity to oncogenic proteins.

In the past there was much speculation as to the existence of tumor antigens because the molecular etiology of cancer was a mystery. The molecular changes associated with malignant transformation have now either been defined or are definable by current methods. Malignant transformation is the end result of alter­ ed expression of genes related to normal cell growth control and differentiation. Altered expression results from a variety of mechanisms including gene amplifi­ cation. somatic DNA mutation and gene translocation. Each mechanism results in the expression of proteins that have the potential to serve as tumor antigens and thus as targets for T ce1t therapy. Gene amplification results in the expression of normal proteins but in markedly increased amounts. Overexpression of individual proteins can result in peptides from that protein being presented in higher concentrations by MHC molcecules. An essential component of the immune system is that many epitopes of proteins are 'ignored'. An increase in the expression of a protein and the resultant increase in the MHC presentation of peptides can render a non-immunogenic protein immunogenic. Overexpressed oncogenic proteins offer the possibility of many tar­ get peptides potentially recognizable by all individuals, The disadvantage is that such proteins are self proteins and that normal mechanisms of immunologic toler­ ance to"'self might prevent the induction of an immune response. Elicitation and augmentation of an immune response to such self proteins, to the extent necessary to eradicate malignant tissue in the body, might also partially or totally destroy the normal tissues that express small amounts of the same protein. DNA mutation of cancer-related genes can result in the expression of altered proteins containing as few as a single amino acid residue different than normal.