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  • Title: A method for the production of CD4+ chronic myelogenous leukemia-specific allogeneic T lymphocytes.
    Author: Serody JS, Brecher ME, Dent G, Bentley SA, Frelinger JA, Shea TC.
    Journal: Cancer Res; 1997 Apr 15; 57(8):1547-53. PubMed ID: 9108458.
    Abstract:
    The graft-versus-leukemia effect is critical to the maintenance of remission in patients transplanted for the treatment of chronic myelogenous leukemia (CML). A pivotal issue in transplantation for CML is whether donor lymphocytes are specific for host tumor or myeloid cells or a subset of the lymphocytes that cause graft-versus-host disease. We have enrolled seven patients in an experimental trial to evaluate the specificity of HLA-matched donor lymphocytes in vitro. We have produced 11 CD4+ cytotoxic and proliferative T-cell clones from five of the donors that only lyse or proliferate to leukemic myeloid cells. These T lymphocytes do not react with interleukin (IL)-2-stimulated blasts, natural killer-sensitive targets, donor neutrophils, or bcr-abl+ EBV-lymphoblastoid cell lines. We show that the addition of the cytokines IL-7 and IL-12 during the production of T-cell clones enhances the recovery of myeloid-specific clones in vitro. Five of the myeloid-specific clones that we produced maintained specificity over 12 weeks in culture. Adoption of this method should allow for the expansion and in vivo testing of CML-specific CD4+ T-cell clones in adoptive immunotherapy.
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