Abstract
Use of LAK cells with interleukin-2 (IL2) in patients with metastatic cancers has shown some response with many side effects (i.e., extravascular fluid extravasation, anemia, fever, rash, diarrhea). To define the mechanism of target cell lysis and explain some of these side effects, we investigated the target structures of LAK cells. Cell lines were used as targets for LAK lysis in a 4 hr. chromium-51 release assay. Cell surface antigens on targets (i.e., Ia2, Fc79, TR) were determined by immunoflourescence with their respective monoclonal antibodies. Results show that TR, which is present on many transformed cells, and more significantly, on some normal cells, is a target of LAK cytotoxicity. Tumor cell lines (K562, Daudi) used as targets for LAK lysis (both >60% lysed) express TR (>50%+). In contrast, blasts of 3 children with ALL did not express TR (<10%+) and were poorly lysed by LAK cells (<25%), while blasts of an adult ALL patient expressing TR (72.7%+) were 60.6% lysed. Normal bone marrow cells (36% TR+), endothelial cells (71.4%TR+) and fibroblasts (83.3%TR+) were all lysed (44.3%, 64.9%, and 31.7% respectively), and normal lymphocytes (<5% TR+ and 27, lysed) could be induced to express TR by Con A stimulation with concomittant increase in LAK lysis (34% TRH- and 31.4% lysis-day #3 in culture). Thus, results show that LAK cells can lyse not only tumor cells, but also normal cells expressing TR. This may explain the anemia and extravascular fluid leakage associated with LAK-IL2 immunotherapy.
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Massey, G., Mohanakumar, T. LYMPHOKINE-ACTIVATED KILLER (LAK) CELLS LYSIS OF NORMAL AND NEOPLASTIC CELLS EXPRESSING TRANSFERRIN RECEPTORS(TR). Pediatr Res 21 (Suppl 4), 302 (1987). https://doi.org/10.1203/00006450-198704010-00807
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DOI: https://doi.org/10.1203/00006450-198704010-00807