THE MULTI-EPITOPE APPROACH FOR IMMUNOTHERAPY FOR CANCER - IDENTIFICATION OF SEVERAL CTL EPITOPES FROM VARIOUS TUMOR-ASSOCIATED ANTIGENS EXPRESSED ON SOLID EPITHELIAL TUMORS

One approach to development of specific cancer immunotherapy relies on the induction of cytotoxic T lymphocytes (CTL) specific for tumor-ass ociated antigens (TAA). Induction of TAA,specific CTL could be used to wards the eradication of established rumors, or to prevent their disse mination or recurrence after primary treatment. The present study iden tifies a set of CTL epitopes from TAA frequently found on solid epithe lial tumors such as breast, lung and gastro-intestinal tumors. Specifi cally, HLA-A2.1 binding peptides from the MAGE2, MAGE3, HER-2/neu and CEA antigens were rested for their capacity to elicit in vitro anti-tu mor CTL using lymphocytes from normal volunteers and autologous dendri tic cells as antigen-presenting cells. A total of 6 new epitopes (MAGE 2[10(157)], MAGE3[9(112)],CEA[9(691)], CEA[9(24)], HER2[9(435)] and HE R2[9(5)]) were identified which were capable of specifically recognizi ng tumor cell lines expressing HLA-A2.1 and the corresponding TAA. In one case (CEA[9(24)]), induction of vigorous anti-rumor CTL responses required epitope engineering to increase HLA-A2.1 binding affinity. Fi nally, most of the newly identified epitopes (5 our of 6) were found t o be highly crossreactive with other common HLA alleles of the A2 supe rtype (A2.2, A2.3, A2.6 and A6802), thus demonstrating their potential in providing broad and non-ethnically biased population coverage. The results are discussed in the context of the development of multi-epit ope-based therapies with broad applicability for patients suffering fr om commonly found rumors. (C) American Society for Histocompatibility and Immunogenetics, 1998. Published by Elsevier Science Inc.