Cytotoxic effects on viable human leukemic cells by combinations of lymphokine activated killer cells and monoclonal antibodies.
Earlier studies with individually phenotyped monoclonal antibody combinations and complement or lymphokine activated killer (LAK) cells showed that many acute myeloid leukemic cells were resistant to these cytotoxic agents when used singly. Therefore, a combination of both agents was studied. When the leukemic target cells were submitted to killer cells activated with 100 or 800 IU of recombinant interleukin-2 (rIL-2), only averages of 6.0 and 16.7% of the targets were killed respectively. When the remaining, refractory cells were confronted with a cocktail of individually phenotyped monoclonal antibodies and complement, an additional significant cell kill was obtained, but it amounted to only between 7.4 and 5.5% (for LAK-100 and LAK-800, respectively). In contrast, of the target cells initially refractory to the same cocktail of monoclonal antibodies, all were cross-resistant both to LAK-cells activated with 100 and to those activated with 800 IU of rIL-2. This cross-resistance was caused neither by sub-optimal LAK-cell activation, nor by antibody blocking of hypothetical LAK-cell receptors, since pre-incubation with monoclonal antibodies without complement did not inhibit LAK-cell cytotoxicity. Although only partial cross-resistance was found in the present study, it still remains that only a minority of the tumor cells could be killed. A higher in-vitro cell kill should be attempted prior to clinical trials in order to avoid clinical effects resembling those of a partial surgical tumor resection.
Vasilopoulos
G
G
Hematology Laboratory, Karolinska Hospital and Institute, Stockholm, Sweden.
Sjögren
A M
AM
Reizenstein
P
P
D000911:Antibodies, Monoclonal; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology*; D008222:Lymphokines / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D008222:Lymphokines; D003165:Complement System Proteins