Retroviral-mediated IL-2 gene transfer into murine neuroblastoma

We used retroviral-mediated gene transfer of the human interleukin (IL)-2 g ene into murine neuroblastoma cells to investigate whether locally-secreted IL-2 is able to influence the generation of anti-tumor immune responses. S upernatant obtained from cultures of approximately 1 x 10(6) IL-2 gene-tran sduced, 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 v ivo, IL-2-secreting neuro-2a cells were s.c. injected into A/J mice and tum or growth was measured weekly. And to estimate whether IL-2 transfected neu roblastoma 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 m ice. Seven days after IL-2 gene-transfected neuroblastoma cell injection, u nmodified 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 ef fect 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 inj ected with IL-2-secreting neuro-2a cells developed tumors within 6 weeks, w hile all of the mice injected with wild-type neuro-2a cells developed tumor s. Immunization of mice with IL-2 gene-transfected, irradiated neuro-2a cel ls protected these animals against a subsequent challenge with wild-type tu mor cells. Finally, the size of large neuroblastomas decreased after IL-2-s ecreting neuro-2a cell injection into mice. Local secretion of IL-2 gene-tr ansduced tumor cells abrogates their tumorigenicity and induces protective immunity and may inhibit the growth of neuroblastoma.