A NATURALLY-OCCURRING MUTANT HUMAN EPIDERMAL GROWTH-FACTOR RECEPTOR AS A TARGET FOR PEPTIDE VACCINE IMMUNOTHERAPY OF TUMORS

The type III EGF receptor (EGFRvIII) is the result of an in-frame dele tion from nucleotides 275 to 1075 in the EGF receptor cDNA sequence cr eating a novel epitope at the fusion junction. This spontaneously occu rring alteration is found in a high percentage of primary human brain, breast, lung and ovarian tumors, We have explored whether a peptide d erived from the fusion junction could serve as the basis for an antitu mor vaccine. Preimmunization of mice with this peptide substantially i nhibited tumor formation by cells expressing EGFRvIII, Tumor cell inoc ulation followed by immunization could also enhance the regression of existing tumors, Antibody production was elicited in animals that was highly specific for the novel epitope and also a CTL response that was mediated by CD8(+) T lymphocytes. The alteration present in EGFRvIII could serve as the basis for an antitumor vaccine with potentially wid e application in humans.