A METHOD FOR THE PRODUCTION OF CD4-SPECIFIC ALLOGENEIC T-LYMPHOCYTES(CHRONIC MYELOGENOUS LEUKEMIA)

The graft-versus-leukemia effect is critical to the maintenance of rem ission in patients transplanted for the treatment of chronic myelogeno us leukemia (CML). A pivotal issue in transplantation for CML is wheth er donor lymphocytes are specific for host tumor or myeloid cells or a subset of the lymphocytes that cause graft-versus-host disease, We ha ve enrolled seven patients in an experimental trial to evaluate the sp ecificity of HLA-matched donor lymphocytes in vitro. We have produced 11 CD4+ cytotoxic and proliferative T-cell clones from five of the don ors that only lyse or proliferate to leukemic myeloid cells, These T l ymphocytes do not react with interleukin (IL)-2-stimulated blasts, nat ural killer-sensitive targets, donor neutrophils, or bcr-abl+ EBV-lymp hoblastoid cell lines, We show that the addition of the cytokines IL-7 and IL-12 during the production of T-cell clones enhances the recover y of myeloid-specific clones in vitro, Five of the myeloid-specific cl ones that we produced maintained specificity over 12 weeks in culture, Adoption of this method should allow for the expansion and in vivo te sting of CML-specific CD4+ T-cell clones in adoptive immunotherapy.