Fig. 4: MMAE radiosensitization stimulates immune responses. | Nature Communications

Fig. 4: MMAE radiosensitization stimulates immune responses.

From: Monomethyl auristatin antibody and peptide drug conjugates for trimodal cancer chemo-radio-immunotherapy

Fig. 4

a Mice with B16 tumors treated with ACPP-MMAE and IR per Fig. 3e starting on day 9 post implantation. Tumors harvested on day 19 and immune infiltrates characterized by flow cytometry. Results representative of three independent experiments. b B16 tumors treated as in Fig. 4a, CD8 tumor infiltration quantified by flow cytometry, normalized to untreated tumors, and plotted as mean ± SEM: untreated (n = 18), IR (n = 13), ACPP-MMAE + IR (n = 8), ACPP-MMAE (n = 6), ACPP, CDX3379 (n = 4), CDX3379, CDX3379-MMAE, CDX3379-MMAE + IR (n = 3). Statistical significances calculated using one-way ANOVA with Tukey’s multiple comparisons test. c Mice with B16 tumors treated with ACPP-MMAE and IR per Fig. 3e starting on day 8. Tumors harvested on day 13 and analyzed using NanoString nCounter PanCancer Mouse Immune Profiling panel. Heatmap depicts Z-score of immune signatures, n = 3. d B16 tumors treated as in Fig. 3h starting day 9 post tumor implantation. Tumor infiltrates quantified by flow cytometry and plotted as mean ± SEM, n = 3 (vehicle day 14), n = 4 (all other points). Statistical significance calculated using two tailed t-testing with multiple comparisons. e B16 tumors implanted in WT or RAG1 KO mice on day 0 treated with ACPP-MMAE and IR as in Fig. 3e starting on day 3. Individual tumor volumes plotted, n = 10. Data from WT mice is from Fig. 3e. f Mice given anti-CD8 antibody (10 mg/kg). B16 tumor cells implanted on day 0 and given 10 nmoles ACPP-MMAE and 5 Gy as in Fig. 3e starting on day 3. Data plotted as mean ± SEM, n = 10. Statistical significance calculated using two-way ANOVA with Tukey’s multiple comparisons test. g B16 tumor bearing mice given anti-CD8 antibody and treated with 2.5 nmoles CDX3379-MMAE and 5 Gy as in Fig. 4f. Data plotted as mean ± SEM and statistical significances calculated using two-way ANOVA with Tukey’s multiple comparisons test, n = 10. h MC38 tumor cells implanted on day 0 and mice injected with 10 nmoles ACPP-MMAE and given 3 Gy as in Fig. 3e starting on day 6. On day 59, tumor cured and tumor naïve mice rechallenged with tumors. Individual tumor volumes plotted, n = 10 for all groups except ACPP-MMAE + IR cured, n = 6. Source data in Source Data file.

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