Lymphokine-Activated Killer Cytotoxicity in Neonatal Mononuclear Cells: In Vitro Responses to Tumor Cell Lines from Pediatric Solid Tumors1

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Abstract
The presence of neonatal (cord) lymphokineactivated killer (LAK) cell activity toward natural killer cell resistant Raji and Daudi cell lines has recently been reported from our laboratory. We investigated the future therapeutic use of LAK adoptive immunotherapy by examining LAK in vitro cytotoxicity from both neonatal and adult mononuclear cells against solid tumor cell lines of relevance to pediatric oncology: SH-SY5Y (neuroblastoma), SK-NM-C (neuroblastoma-neuroepithelioma), NEP-1 (Wilms' tumor), SK-ES-1 (Ewing's sarcoma), and A-204 (rhabdomyosarcoma). Cord and adult mononuclear cells were activated by recombinant IL-2 (100 µ/ml) for 5- 7 days and added in an effector:target ratio of 40:1 to 51Crlabeled target cells. Specific cell lysis was determined after a 4-h incubation. There was a significantly high level of cord and adult LAK cytotoxicity against Wilms' (76.4 ± 9.8 versus 77.3 ± 6.8%) and Ewing's (84.2 ± 5.5 versus 71.1 ± 6.5%) cell lines and significant but moderate LAK activity against neuroepithelioma (52.0 ± 6.6 versus 55.4 ± 4.5%) and rhabdomyosarcoma (46.6 ± 5.7 versus 43.9 ± 5.2%) cell lines. There was no difference between cord and adult LAK activity toward these targets. However, a differential response toward the more classical neuroblastoma cell line, SH-SY5Y, was noted with significantly more LAK cytotoxicity from cord mononuclear cells than adult mononuclear cells (51.2 ± 6.9 versus 28.5 ± 8.2%) (p<0.01). These in vitro results suggest that pediatric tumors such as neuroblastoma, Wilms', Ewing's, and possibly rhabdomyosarcoma and neuroblastoma-neuroepithelioma may be good candidates for future LAK adoptive immunotherapy and that a possible cellular immune mechanism may account for the improved prognosis of advanced neuroblastoma in the neonatal period.