Mimics and cross reactions of relevance to tumour immunotherapy

MUC1 has been used as a target for immunotherapy and with oxidised mannan i n mice there is selective delivery into the class I pathway and the inducti on of a T1 response. We have also been working in pig-to-human transplantat ion and of particular interest is the description in humans of natural Ga1 alpha(1,3)Gal antibodies (Abs) which react with pig tissues. A peptide mimi c (DAHWESWL) to the Ga1 alpha(1,3)Gal sugar was found in a phage display li brary and is also mimicked by MUC1 peptides. It was of interest to note tha t while mice make cytotoxic T cells (CTLs) and little Ab to MUC1, humans ma ke the reverse immune response. It was found that the cross reaction of the natural Ga1 alpha(1,3)Gal Abs in humans to MUC1 was likely to be responsib le for the diversion. Cross reactions are therefore an important problem in tumour immunotherapy, although the problem can be overcome by in vitro imm unisations. (C) 1999 Elsevier Science Ltd. All rights reserved.