In vitro cytolysis of primitive neuroectodermal tumors of the posterior fossa (medulloblastoma) by lymphokine-activated killer cells.
Short-term stimulation of nonantigen-primed peripheral blood mononuclear leukocytes with interleukin-2 generates a population of oncolytic effectors designated "lymphokine-activated killer" (LAK) cells. These LAK cells express potent lytic activity against a wide spectrum of fresh or cultured autochthonous (patient's own) and allogeneic (unrelated) tumors, yet specifically spare normal tissues. In this study, cells derived from primitive neuroectodermal tumors of the posterior fossa (PNET-PF) were examined for their sensitivity to LAK cytolysis utilizing an in vitro 4-hour chromium-51-release assay. Five early-passage cell lines, derived from primary PNET-PF, demonstrated significant sensitivity to LAK cell cytolysis. Lysis was equally effective in culture medium and cerebrospinal fluid. Three freshly excised PNET-PF exhibited similar susceptibility to lysis by autochthonous LAK cells. Greatly increased expansion of LAK cell cultures could be achieved by short-term stimulation with monoclonal anti-CD3 antibodies in addition to interleukin-2 activation. These findings constitute the preliminary in vitro foundations for potential intrathecal adoptive immunotherapy of PNET-PF with LAK cells.
George
R E
RE
Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.
Loudon
W G
WG
Moser
R P
RP
Bruner
J M
JM
Steck
P A
PA
Grimm
E A
EA
D000328:Adult; D002528:Cerebellar Neoplasms / Q000276:immunology / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D066298:In Vitro Techniques; D007223:Infant; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008527:Medulloblastoma / Q000276:immunology / Q000473:pathology*
D007376:Interleukin-2