Tumor Vaccine Effect by IL-16 Gene Transfer into Murine Neuroblastoma Model

Cho, Hyun Sang; Park, Chong Young

Abstract

PURPOSE: Interleukin(IL)-16 is a potent chemoattractant factor for CD4+ T cells, monocytes, and eosinophils. It up-regulates IL-2R on CD4+ T lymphocytes and regulates the function of antigen presenting cells. We used retrovirus-mediated gene transfer of the human IL-16 gene into the neuro-2a cells, which is the murine neuroblastoma cell lines, to investigate whether locally secreted IL-16 might generate anti-tumor immune responses.
METHODS
We estimated whether the local secretion of IL-16 from the genetically-modified tumor cells would affect their tumorigenicity in vivo, and then, IL-16 transfected neuroblastoma cells would protect mice from tumor development after wild-type tumor cell challenges. And we investigated the mechanism of IL-16 by nude mice trial of an anti-tumor immune response.
RESULTS
The IL-16 gene-transduced neuro-2a clones secreted 4.2-6.0ng of IL-16 per mL per 10(5) cells during 24 hr. None of the mice(N=6) injected with 2x10(6) of irradiated, IL-16 gene-transfected neuro-2a cells developed tumors within 6 weeks while all of the mice(N=6) injected with wild-type neuro-2a cells developed tumors. Immunization of mice(N=6) with 2x106 IL-16 gene- transfected, irradiated neuro-2a cells protected these animals against a subsequent challenge with 2x10(6) wild-type tumor cells. Nude mice also showed an anti-tumorigenicity effect. However, the mice did not reveal the prophylactic effect against murine neuroblastoma.
CONCLUSION
The local secretion of IL-16 gene-transduced tumor cells abrogated their tumorigenicity and induced protective immunity.