Efficacy of B16 Melanoma Cells Exposed In Vitro to Long-Term IFN-α Treatment (B16α Cells) as a Tumor Vaccine in Mice

Abstract

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.

Tumor vaccine composed of C-class CpG oligodeoxynucleotides and irradiated tumor cells induces long-term antitumor immunity

“…These results suggested that the repeated vaccination was more effective in generating a durable antitumor response than a single vaccination. Similarly, in the study of Wu and Fleischmann, it was reported that after repeated vaccination of mice with a tumor vaccine (composed of irradiated B16 melanoma cells exposed in vitro to long-term IFN-alpha treatment) a protective durable immunity against a second tumor challenge was significantly increased [21,22]. Our results are also in agreement with the statements of other authors that short-term or weak antigen stimulation can trigger the initial proliferation of effector T cells but is insufficient to trigger the long-lived memory T cells [23-25].…”

Enhancing CTL responses to melanoma cell vaccines in vivo: synergistic increases obtained using IFNγ primed and IFNβ treated B7‐1+ B16‐F10 melanoma cells

“…Other studies have reported that B16 cells pretreated with IFNα alone stimulated immune responses when the IFN treated cells were used as immunotherapeutic vaccines 24 , 25 . The protective antitumour effects correlated with the induction of an enhanced host immune response as depletion of macrophages and CD8 + CTL in the immunized mice reversed the effect 24 .…”

The designer cytokine hyper-IL-6 mediates growth inhibition and GM–CSF-dependent rejection of B16 melanoma cells

“…H-2K b expression of B16 cells was shown to be downregulated but inducible after IFN-a treatment (Wu and Fleischmann, 1998). To investigate whether H-IL-6 expression in¯uenced cell surface expression of H-2K b of B16 cells we performed ow cytometric analysis using anti-H-2K b -antibody.…”