Injury to autologous normal tissues and tumors mediated by lymphokine-activated killer (LAK) cells generated in vitro from peripheral blood mononuclear cells of glioblastoma patients

Activation of peripheral blood mononuclear cells (PBMC) with IL-2 generates lymphokine-activated killer (LAK) cells that show a broad target cell rang e. In adoptive immunotherapy using in vitro-generated LAK cells, the intens ity and specificity of their cytotoxic activity affect the prognosis of can cer patients. The present study was designed to examine the tumor-specific spectrum of T lymphocytes generated from the PBMC of patients with recurren t glioblastoma by in vitro propagation with IL-2 plus either soluble or sol id-phase anti-CD3 monoclonal antibody (MAb) in short-term or long-term cult ures. Both short-term and long-term culturing with solid-phase anti-CD3 MAb plus IL-2 yielded broad-reactivity CD8(+) alpha beta T and gamma delta T l ymphocytes, both of which were non-MHC restricted, as shown by the fact tha t they were able to lyse autologous glioblastoma cells, MHC class I+II- all ogeneic glioblastoma cells, and MHC class I-II-NK-sensitive K562 target cel ls. More importantly, these cells from patients failed to lyse fresh autolo gous PBMC. These results demonstrate that cells generated using this approa ch are non-MHC-restricted LAK cells and exhibit marked tumor specificity. I n contrast, incubation with soluble anti-CD3 MAb generated T lymphocytes th at after long-term culture, were either CD4(+) or CD8(+). These caused sign ificant lysis of both allogeneic and autologous glioblastoma target cells, the extent of lysis being greater than that using cells produced by culturi ng with the solid-phase MAb. However, both the CD4(+) and CD8(+) cells also caused greater lysis of autologous normal PBMC, indicating that cells gene rated using this approach may cause significant adverse reactions in cancer patients if used for immunotherapy.