Activation of autologous lymphocytes of patients with chronic myelogenous leukemia in the chronic phase with cytokines and CD3 monoclonal antibody results in bcr/abl⁺ blood leukocyte cultures as determined by reverse transcriptase-polymerase chain reaction

To investigate the potential of autologous lymphocytes to eliminate chronic myelogenous leukemia (CML) cells following activation and targeting by CD3-monoclonal antibody, we cultured Ficoll-isolated peripheral blood cells from 11 patients with CML in the chronic phase in permutated combinations of interleukin (IL)-2, CD3-monoclonal antibody (OKT3), and interferon (IFN)γ. The efficiency of CML cell elimination was studied by means of flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Cultures containing only OKT3 and IL-2, with or without IFNγ, resulted in tumor cell reduction to the level of RT-PCR negativity. The length of the culture period required to reach a RT-PCR-negative state ranged from 3 to 33 days. A 1- to 2-log reduction in leukemic cells could be achieved by culture medium alone. In contrast, 3- to 4-log reductions in CML cells were observed following in vitro culture and ex vivo T cell activation with a given sensitivity for RT-PCR detection of 1 bcr/abl⁺ cell in 10⁴. The feasibility of purging chronic myelogenous leukemia cells in a short time was associated with a low number of platelet counts (r = 0.6457; p < 0.05). CML cell reduction was associated with expansion of CD25⁺/CD4(+/-)/CD8(+/- )/CD56(+/-) lymphocytes. These findings may be of relevance for immunotherapy procedures.