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A Method for the Production of CD4+ Chronic Myelogenous Leukemia-specific Allogeneic T Lymphocytes¹

Departments of Medicine, Laboratory Medicine, and Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7305

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.

¹ This work was supported by grants from the University of North Carolina Lineberger Comprehensive Cancer Center (to J. S. S.) and NIH Grants CA 66715 (to J. S. S.) and AI 20288 (to J. A. F.).

² To whom requests for reprints should be addressed, at Program in Bone Marrow Transplantation, Department of Medicine, CB #7305, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7305. Phone: (919) 966-6975; Fax: (919) 966-7748.

Received 10/30/96. Accepted 2/17/97.

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