Interleukin-2 and lymphokine activated killer (LAK) cells in the treatment of malignant glioma: clinical and experimental studies.
The phenomenon of glioma killing by lymphokine activated killer cells (LAK) was studied. We demonstrate that LAK cells generated by culturing the lymphokine interleukin-2 (IL-2) with peripheral blood lymphocytes from brain tumour patients destroys autologous glioma. The rat 9L glioma model was used to show that LAK killing was tumour-selective as glioma but not syngeneic normal brain tissue was destroyed. The susceptibility of both human and 9L rat glioma to LAK cell killing was markedly diminished by pretreating glioma cells with trypsin or chymotrypsin, but was unaffected by pretreatment with neuraminidase, glycosidases, sodium periodate or hydrocortisone. These results suggest that the cell surface determinant on glioma cells responsible for its tumour selective lysis by LAK is a protein sensitive to trypsin and chymotrypsin. The tumour-selective killing of glioma by LAK in vitro prompted the initiation of a Phase I study in which ten patients with malignant glioma have been treated with direct intracerebral injection of IL-2 or LAK without evidence of systemic or brain toxicity.
D000328:Adult; D000368:Aged; D000818:Animals; D001894:Borohydrides / Q000494:pharmacology; D001932:Brain Neoplasms / Q000628:therapy*; D002460:Cell Line; D002918:Chymotrypsin / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D005910:Glioma / Q000628:therapy*; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010504:Periodic Acid / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D014357:Trypsin / Q000494:pharmacology
D001894:Borohydrides; D007376:Interleukin-2; D010504:Periodic Acid; C009288:metaperiodate; D002918:Chymotrypsin; D014357:Trypsin