Original communicationSynergistic effect of intratumoral IL-12 and TNF-α microspheres: systemic anti-tumor immunity is mediated by both CD8+ CTL and NK cells
Section snippets
Animals and tumors
Six- to 8-week old female C57Bl6 mice were purchased from the Jackson Laboratory (Bar Harbor, NE) and maintained in specific pathogen-free conditions at the Animal Maintenance Facility of the University of Michigan Medical Center. MCA205 is a poorly immunogenic fibrosarcoma cell lines induced by 3-methylcholanthrene and syngeneic to C57Bl6 mice.7, 8 B16-BL6 (B16) is also a poorly immunogenic cell line; a melanoma of spontaneous origin that has been studied extensively.9 Cell lines were
Intratumoral injection of IL-12 and TNF-α microspheres confers systemic Anti-Tumor immunity
The synergy between IL-12 and TNF-α in MCA205 bearing C57Bl6 mice in generating a systemic anti-tumor response was confirmed via ELISPOT assay of the splenocytes to quantify tumor-specific IFN-γ producing cells (Fig 1). IL-12 alone did result in a significant increase in tumor specific T-cells compared to mice treated with BSA loaded microspheres or surgical excision. However, splenocytes from mice treated intralesionally with IL-12 and TNF-α demonstrated a dramatic increase in MCA205 specific
Discussion
Research in immunotherapy has focused on the post-operative setting, which is caught in a catch-22. The most immunogenic approaches have been those that utilize autologous tumor or tumor-infiltrating lymphocytes, but these approaches require an adequate amount of harvestable tumor, limiting their applicability to those patients with advanced disease. Approaches that are more clinically feasible in patients with only microscopic residual disease, such as peptide or allogeneic cellular vaccines,
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Funded in part by NIH Grant CA102602-01 and a grant from the Gillson-Longenbaugh Foundation.