Efficacy of B16 Melanoma Cells Exposed in Vitro to Long-term IFN-alpha Treatment (B16alpha Cells) As a Tumor Vaccine in Mice
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B16 melanoma cells exposed to >2 weeks of in vitro interferon-alpha (IFN-alpha) treatment (B16alpha cells) were UV inactivated and used for vaccination. This vaccination was efficacious against challenge with parental B16 cells in the absence of adjuvant therapy. Vaccinations based on parental cells and B16 cells exposed to short-term in vitro IFN-alpha treatment were not effective. The efficacy of B16alpha vaccination was evaluated using three B16 tumor models. Using intraperitoneal (i.p.) tumor challenge given after vaccination, vaccination efficacy depended on the concentration of IFN-alpha to which B16alpha cells were exposed, the number of inactivated B16alpha cells inoculated, the number of inoculations administered, and the amount of tumor burden. A significant fraction (30%) of vaccinated mice surviving initial challenge had durable immunity against a second parental tumor challenge. This immunity increased to 92% with administration of a single booster vaccination. Using metastatic tumor challenge given after vaccination, vaccination reduced lung metastases by approximately 67%. Using vaccination begun 3 days after subcutaneous (s.c.) tumor challenge, regression of established tumor occurred when vaccination was given i.p. (39%) or contralaterally s.c. (53%). Taken together, the results suggest that vaccination with inactivated B16alpha cells may serve as a model for induction of host tumor immunity against primary or secondary tumors.
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