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. 2023 Apr 18;11(7):962–977. doi: 10.1158/2326-6066.CIR-22-0705

Figure 2.

Figure 2. mWTX-330 is preferentially activated in the TME and has a greater therapeutic window than chimeric IL-12. A and B, Plasma (A) and tumor (B) samples from MC38 tumor-bearing mice treated with mWTX-330 were analyzed at various timepoints for either the presence of the total INDUKINE protein (tan) or free chimeric IL-12 (red). The AUC was calculated, and the ratio of total INDUKINE molecule to free chimeric IL-12 was calculated. C, MC38 tumor-bearing mice were dosed twice with mWTX-330, and the frequency of polyfunctional CD8+ T cells in the tumor, peripheral blood, tumor draining or nontumor draining lymph nodes was measured by examining coexpression of IFNγ, TNF, and Granzyme B after PMA/ionomycin restimulation. D, Representation of the therapeutic window of recombinant chimeric IL-12 or mWTX-330 in MC38 tumor-bearing mice based on multiple experiments identifying the MED and the MTD of each molecule (Supplementary Fig. S3). Where applicable, error bars represent the mean (± SD).

mWTX-330 is preferentially activated in the TME and has a greater therapeutic window than chimeric IL-12. A and B, Plasma (A) and tumor (B) samples from MC38 tumor-bearing mice treated with mWTX-330 were analyzed at various timepoints for either the presence of the total INDUKINE protein (tan) or free chimeric IL-12 (red). The AUC was calculated, and the ratio of total INDUKINE molecule to free chimeric IL-12 was calculated. C, MC38 tumor-bearing mice were dosed twice with mWTX-330, and the frequency of polyfunctional CD8+ T cells in the tumor, peripheral blood, tumor draining or nontumor draining lymph nodes was measured by examining coexpression of IFNγ, TNF, and Granzyme B after PMA/ionomycin restimulation. D, Representation of the therapeutic window of recombinant chimeric IL-12 or mWTX-330 in MC38 tumor-bearing mice based on multiple experiments identifying the MED and the MTD of each molecule (Supplementary Fig. S3). Where applicable, error bars represent the mean (± SD).