Chronic Myelogenous Leukaemia Antigens

Mildred Scheel Foundation 10-1173-Pa3

Accumulating data suggest that CML is immunogenic for the host´s immune system and imply that enhancing the anti-tumour immune response by specific active and adoptive immunotherapy may be of clinical value in treating the disease. The present project will continue to explore the role of bcr/abl and abl/bcr, as well as WT-1-derived, peptides as immunogens for CML patients T cells, in pre-clinical studies. We have previously recently identified immunogenic bcr/abl peptides and recently also abl/bcr (and WT-1) peptides. We intend to construct soluble MHC/peptide tetramers using these and other novel tumour antigens. These will be used to quantify antigen-reactive cells in normal donors and patients, isolate them and expand them in tissue culture to numbers applicable for adoptive immunotherapy. Other novel tumour antigens will be identified using T cells sensitised in cytokine-modified autologous mixed lymphocyte/tumour cell cultures. Such sensitised T cells will be used to detect the presence of antigenic peptide in fractionated peptide mixtures eluted from CML cell eluates, and then sequenced. T cells specific for the above antigens may not have a long life expectancy in tissue culture and therefore ways of extending this will be sought. In particular, expression of the catalytic component of human telomerase will be enforced in these cells in an attempt to extend their normal lifespan.