Culture, characterization, and cytotoxic activity of gammadelta T cells from patients with Ph(+) chronic myeloid leukemia: A potential role in cell therapy

TCR γδ T cells are a small subset of T lymphocytes that possess potent anti-tumor activity. This thesis is concerned with exploring the potential therapeutic role of γδ T cells in Ph(+) Chronic Myeloid Leukemia (CML). The thesis describes the isolation and characterization of cultured γδ T cells derived from patients with Ph(+) CML and assesses their cytotoxicity to CML target cells. A clinical trial has also been designed and a protocol prepared using autologous γδ T cells administered after autotransplant for Ph(+) CML. Our laboratory results show that large quantities of γδ T cells derived from the peripheral blood of Ph(+) CML patients can be increased many thousands fold in vitro. These cells exhibit abnormal growth patterns in culture compared with γδ T cells from normal controls grown under the same culture conditions. In contrast, γδ T cells from the same CML patients have normal growth characteristics in vitro. Cytogenetic and molecular analysis showed that γδ T cells cultured from CML blood were Ph(−) and hence not part of the leukemic clone. Of interest, minor clonal chromosomal abnormalities involving the immunoglobulin heavy chain and TCR genes were detected in cultured γδ but not αβ T cells from CML patients. γδ T cells were cytotoxic against K562 cell line and preliminary evidence suggests specific cytotoxic activity against Ph(+) autologous early hematopoietic progenitors.