Fig. 3: MMAE radiosensitizes syngeneic murine tumors. | Nature Communications

Fig. 3: MMAE radiosensitizes syngeneic murine tumors.

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

Fig. 3

a B16 cells treated with MMAE and analyzed by ApoTox-Glo Triplex Assay. Data plotted as mean ± SD, n = 3. b For clonogenic survival, B16 cells treated with MMAE, colony number normalized and plotted as mean ± SEM, n = 11 (0, 1, 5 10, 50 nM), n = 5 (2, 100 nM). Statistical significances calculated using one-way ANOVA with Tukey’s multiple comparisons test. c Cell cycle analysis of MMAE-treated B16 cells. Data plotted as mean ± SD, n = 2. d Clonogenic survival of B16 cells treated with MMAE and 2 Gy. Data plotted as mean ± SEM, n = 6. Statistical significances calculated using one-way ANOVA with Sidak’s multiple comparisons test. e Treatment scheduling MMAE + IR in subcutaneous tumors. Tumor cells implanted on day 0. Treatment started on day 3 for LL/2 and B16 and day 6 for MC38 tumors. 10 nmoles ACPP-MMAE injected for 2 doses. IR given on 3 consecutive days, 5 Gy/day (LL/2, B16) and 3 Gy/day (MC38). Mouse survival plotted and statistical significances (ACPP-MMAE + IR vs. ACPP-MMAE) calculated using Log-rank (Mantel–Cox) test, n = 5. f Tumor-bearing mice injected with 10 nmoles of ACPP-MMAE, n = 12 (LL/2) n = 8 (B16). Tumors harvested, drug concentration scatter plot with mean ± SEM. g 4NQO carcinogen-induced tongue model. At week 20 after 4NQO exposure, mice injected with 10 nmoles ACPP-MMAE × 2 doses. Whole tongue IR given as 5 Gy × 2. Tongues resected at week 22, H&E stained, and tumors quantified. Representative whole and sectioned untreated tongues (tumors indicated by black arrows). Mean tumors/tongue ± SEM plotted, n = 7 (untreated), n = 6 (IR), n = 8 (ACPP-MMAE, ACPP-MMAE + IR). Statistical significances calculated using one-way ANOVA with Tukey’s multiple comparisons test. h Mice implanted with B16 tumor cells on day 0 and treated as in Fig. 3e except for 2.5 nmole dose of ADC. Mouse survival plotted and statistical significance (CDX3379-MMAE + IR vs. CDX3379-MMAF + IR) calculated using Log-rank (Mantel–Cox) test, n = 5. i Chemical structure of auristatins with moieties altering cell permeability circled. Results in (a, c) representative of 2 independent experiments. Source data provided in Source Data file.

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