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)gamma. 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 IFNgamma, 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 10(4). 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.
Krackhardt
A
A
Department of Hematology, Oncology and Transfusion Medicine, Medical School Benjamin Franklin, Free University Berlin, Germany.
Maurer
J
J
Thiel
E
E
Notter
M
M
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology*; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D016315:Proto-Oncogene Proteins c-abl / Q000032:analysis*; D051562:Proto-Oncogene Proteins c-bcr; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr