Yonsei Med J.  2000 Feb;41(1):76-81. 10.3349/ymj.2000.41.1.76.

Retroviral-mediated IL-2 gene transfer into murine neuroblastoma

• Cho HS
• Song JY
• Park CY
• Lyu CJ
• Kim BS
• Kim KY

• KMID: 1060275
• DOI: http://doi.org/10.3349/ymj.2000.41.1.76

Abstract

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.

Keyword

Interleukin-2; neuroblastoma

MeSH Terms

Animal
Antibody Formation
Gene Transfer Techniques*
Human
Immunization/methods
Interleukin-2/therapeutic use
Interleukin-2/genetics*
Mice
Neoplasm Transplantation
Neuroblastoma/therapy
Neuroblastoma/prevention & control
Neuroblastoma/pathology
Neuroblastoma/genetics*
Retroviridae/genetics*
Tumor Cells, Cultured