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ISOLATED ANTIGENIC ONCOGENE PEPTIDE FRAGMENTS AND USES
An isolated antigenic peptide fragment that is an isolated oncogene protein fragment is disclosed. The isolated peptide fragment of the invention is a peptide either 9 or 10 amino acid residues in length that includes at least a leucine residue at the C- terminus (i.e., position 9 or position 10). The peptide fragment is capable of binding in an HLA-A2 binding cleft and is capable of stimulating proliferation of at least one tumor-specific cytotoxic T-lymphocyte. Preferred peptides further include an isoleucine residue at position 2 and a valine residue at position 6. The most preferred isolated peptides can stimulate proliferation of cytotoxic T-lymphocytes obtainable from peripheral blood lymphocytes, ovarian tumors, breast tumors, gastric tumors, non-small cell lung tumors, pancreatic tumors, colon tumors, gliomas, bladder tumors, endometrial tumors and neuroblastomas. The preferred isolated peptide of the invention is a mutant peptide defined by SEQ ID NO.:2 or its functional equivalents.Isolated cytotoxic T-lymphocytes capable of recognizing isolated peptides of the invention, particularly the HER2/neu mutant peptide are disclosed. These lymphocytes are especially useful for killing tumors or other cells which present on their surfaces the antigenic peptides of the invention. In particular, the lymphocytes are obtainable from ovarian tumor cells, breast tumor cells and non-small-cell lung tumor cells.A method of stimulating proliferation of tumor-specific cytotoxic T-lymphocytes is described. This method includes obtaining lymphocytes from tumor tissue and contacting the lymphocytes with a peptide of the invention under conditions sufficient for the cytotoxic T-lymphocytes to proliferate. Therapeutically effective compositions containing the HER2/neu peptides are also described.
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Inventor(s):EBERLEIN, T.; PEOPLES, G.; YOSHINO, I.; GOEDEGEBUURE, P.