CD38-targeted attenuated interferon alpha immunocytokine activates both innate and adaptive immune cells to drive anti-tumor activity
Fig 6
Treatment with mCD38-mAtt induces the proliferation and activation of CD8 T cells.
Immunocompetent BALB/c mice were inoculated with CT26 tumor cells, and once tumors reached an average volume of ~ 300 mm3, mice were administered vehicle or mCD38-mAtt, at 10 or 30 mg/kg. Six days post treatment initiation, mice were euthanized, and tumors were collected. Proliferation of CD8 T cells was measured by Ki67 staining A, expressed as a percentage of total tumor CD8 T cells. B, The ratio of CD8:Tregs within tumors was also assessed. C–E, Immunocompetent BALB/c mice were inoculated with CT26 tumor cells, and once tumors reached an average volume of ~ 300 mm3, mice were administered vehicle, 2 mg/kg mIFNα, or 10 mg/kg mCD38-mAtt, and tumors were harvested 7 days post treatment. C, Tumor antigen AH1-specific CD8 T cells were measured by dextramer staining and are expressed as a percentage of total tumor CD8+ T cells. D, Dissociated tumor cells were stimulated ex vivo with or without AH1 peptide. The frequency of AH1-specific cells producing granzyme B was assessed by subtracting the background (percentage of granzyme B+ cells without AH1 restimulation) from AH1-stimulated cells. Correlation between the number of granzyme B+ E, AH1-specific, or F, non-specific CD8 T cells with tumor mass at the time of take down. Linear regression was used to assess goodness of fit. GzB, granzyme B; mIFNα, murine interferon alpha.