RESUMO
The killing of Fischer rat 9L glioma in vitro by lymphokine-activated killer (LAK) cells was studied. LAK cells generated by culturing Fischer spleen cells with recombinant interleukin 2 markedly lysed glioma cells but did not kill syngeneic normal brain tissue in a chromium release microcytotoxicity assay. Susceptibility of glioma to lysis by LAK cells was markedly diminished by pretreating the glioma cells with trypsin or chymotrypsin but was unaffected by pretreatment with neuraminidase, glycosidases, or sodium periodate. These results suggest that LAK cell killing of glioma is probably tumor-selective and that a crucial cell surface determinant on glioma cells responsible for its tumor-selective lysis by LAK is a protein sensitive to trypsin and chymotrypsin.
Assuntos
Antígenos de Superfície/imunologia , Glioma/imunologia , Interleucina-2/farmacologia , Células Matadoras Naturais/imunologia , Animais , Glioma/terapia , Células Matadoras Naturais/transplante , Ativação Linfocitária , Masculino , Proteínas do Tecido Nervoso/imunologia , Ratos , Baço/imunologiaRESUMO
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.
Assuntos
Neoplasias Encefálicas/terapia , Glioma/terapia , Interleucina-2/uso terapêutico , Células Matadoras Naturais/imunologia , Ativação Linfocitária , Adulto , Idoso , Animais , Boroidretos/farmacologia , Linhagem Celular , Quimotripsina/farmacologia , Citotoxicidade Imunológica , Modelos Animais de Doenças , Feminino , Humanos , Interleucina-2/administração & dosagem , Células Matadoras Naturais/transplante , Masculino , Pessoa de Meia-Idade , Ácido Periódico/farmacologia , Ratos , Ratos Endogâmicos F344 , Tripsina/farmacologiaRESUMO
The killing of human glioma by lymphokine activated killer (LAK) cells was studied. LAK cells generated by culturing recombinant interleukin-2 (IL-2) with human peripheral blood lymphocytes (PBL) obtained from normal volunteers markedly lysed allogeneic glioma grown in tissue culture. Susceptibility of glioma to lysis by LAK cells was abrogated by pretreating the glioma cells with trypsin or chymotrypsin, but was unaffected by pretreatment with hydrocortisone, neuraminidase, glycosidases or sodium periodate. These results suggest that the cell surface determinant on human glioma cells responsible for its tumor selective lysis by LAK is a protein sensitive to trypsin and chymotrypsin.