Retroviral-mediated IL-2 gene transfer into murine neuroblastoma.
We used retroviral-mediated gene transfer of the human interleukin (IL)-2 gene into murine neuroblastoma cells to investigate whether locally-secreted IL-2 is able to influence the generation of anti-tumor immune responses. Supernatant obtained from cultures of approximately 1 x 10(6) IL-2 gene-transduced, G-418 selected neuro-2a cells was assayed for human IL-2 production by ELISA kit. First, to estimate whether the local secretion of IL-2 from the genetically-modified tumor cells would affect their tumorigenicity in vivo, IL-2-secreting neuro-2a cells were s.c. injected into A/J mice and tumor growth was measured weekly. And to estimate whether IL-2 transfected neuroblastoma cells protect mice from tumor development after wild-type tumor cell challenge, IL-2-secreting neuro-2a cells were s.c. injected into A/J mice. Seven days after IL-2 gene-transfected neuroblastoma cell injection, unmodified neuro-2a cells were s.c. injected into the contralateral site of A/J mice and tumor growth was measured weekly. Finally, to estimate IL-2 effect on pre-established large tumor burdens, IL-2-secreting neuro-2a cells were s.c. injected into A/J mice with established tumor and its growth was measured weekly. The IL-2 gene-transduced neuro-2a clones secreted 120.25-177.3 IU of IL-2 per ml per 10(6) cells during 24 hr. None of the mice injected with IL-2-secreting neuro-2a cells developed tumors within 6 weeks, while all of the mice injected with wild-type neuro-2a cells developed tumors. Immunization of mice with IL-2 gene-transfected, irradiated neuro-2a cells protected these animals against a subsequent challenge with wild-type tumor cells. Finally, the size of large neuroblastomas decreased after IL-2-secreting neuro-2a cell injection into mice. Local secretion of IL-2 gene-transduced tumor cells abrogates their tumorigenicity and induces protective immunity and may inhibit the growth of neuroblastoma.
Cho
H S
HS
Department of Pediatrics, Hallym University College of Medicine, Seoul, Korea.
Song
J Y
JY
Park
C Y
CY
Lyu
C J
CJ
Kim
B S
BS
Kim
K Y
KY
D000818:Animals; D000917:Antibody Formation; D018014:Gene Transfer Techniques; D006801:Humans; D007114:Immunization / Q000379:methods; D007376:Interleukin-2 / Q000235:genetics* / Q000627:therapeutic use; D051379:Mice; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control / Q000628:therapy; D012190:Retroviridae / Q000235:genetics*; D014407:Tumor Cells, Cultured
D007376:Interleukin-2