Helper and cytotoxic lymphocyte responses to chronic myeloid leukaemia: implications for adoptive immunotherapy with T cells.

We studied 19 patients with chronic myeloid leukaemia (CML) to characterize T-cell autologous responses to leukaemia. Third party stimulated alloresponses in mixed lymphocyte reactions were normal in all patients. Using the helper T-lymphocyte precursor frequency (HTLPf) assay we demonstrated a low frequency of T helper cells recognizing autologous leukaemia cells from CML blood (1/850 000) and marrow (1/965 000). However, similar frequencies to autologous bone marrow and lymphoid cells were also found in normal individuals. In 11 patients studied, HLA-matched siblings had a higher HTLPf to leukaemia than the patient's autologous response (P < 0.004). Alloresponse in mixed lymphocyte reactions (MLR), and autologous HTLPf to leukaemia, were comparable at all stages of disease progression and time from diagnosis, and independent of treatment given. In order to generate autologous cytotoxic lymphocyte responses to CML, lymphocytes were stimulated with CML cells. Cultures were fed again with CML cells and examined for cytotoxicity after 21 d. Strong lymphokine-activated killer (LAK) cytotoxicity was found against K562 and Daudi cell lines, and to Epstein-Barr virus-transformed allogeneic and autologous lymphoblastoid cell lines. Autologous leukaemia cells were lysed to a lesser extent in only 3/13 patients tested. The findings indicate that immune reactivity in CML is normal but suggest that CML cells are relatively resistant to lysis by cytotoxic T cells. The results do not support the existence of a leukaemia-specific T-cell response in CML.