Extended Data Fig. 6: αCD45-Cytokine therapy eradicates injected tumors.
From: Local delivery of cell surface-targeted immunocytokines programs systemic antitumor immunity
a, Leukocyte fraction calculated from EPIC RNA-seq analysis across all TCGA entries (n = 11070) or TISMO mouse entries (n = 1518). b, Tumor growth curves (left) and weights (right) of C57BL/6 J mice (n = 5/group) inoculated with 106 MC38 tumor cells and treated with IgG-Cyt therapy or αCD45-Cyt therapy as described in Fig. 3a. c, Representative tumor growth curves (left) and weights (right) of C57BL/6 J mice (n = 5 mice /group representative of 3-4 independent experiments) inoculated with 106 B16F10 tumor cells and treated with IgG-Cyt therapy or αCD45-Cyt therapy as described in Fig. 3a. d-h. C57BL/6 J mice (n = 5 in untreated group, n = 5 in IgG-Cyt group, n = 5 in αCD45-Cyt group) inoculated with 106 B16F10 tumor cells were treated with IgG-Cyt or αCD45-Cyt therapy beginning on d7. One day after completing therapy, tumors, TDLNs, axillary draining lymph nodes (AxLN), non-draining contralateral lymph nodes (cLN), and serum were harvested, lysed, and analyzed for cytokine expression. Shown are the analyte concentrations in pg per mg of tissue for d, IFNg e, IL-12p70 f, IL-1b g, GM-CSF and h, IL-6. i, Overall survival of C57BL/6 J mice (n = 6 in PBS cohort, n = 7 in αCD45 group) bearing B16F10 tumors treated with αCD45 (in the absence of cytokine) on an identical regimen and molar matched dose to that described in Fig. 3a. j, Overall survival of C57BL/6 J mice cured of MC38 tumors rechallenged with 105 MC38 cells 100 days after the initial challenge. k, Overall survival of C57BL/6 J mice (n = 5/group) inoculated with 106 B16F10 tumor cells and treated with IL-12 immunocytokine monotherapy (1 µg dose) or IL-15 immunocytokine monotherapy (10 µg dose) as shown on the diagram. l, Tumor growth curves of C57BL/6 J mice (n = 5/group representative of 2 independent experiments) inoculated with 106 B16F10 cells and treated systemically (i.p.) with αCD45-Cyt therapy with the same doses and schedule as in Fig. 3a. m, Weights of mice shown in l. n, Overall survival of mice shown in l across 2 independent experiments (n = 10 in all groups). o, Tumor growth curves of C57BL/6 J mice (n = 5 in all treatment groups) inoculated with 106 B16F10 cells and treated with the full αCD45-Cyt intratumorally, peritumorally, or the IL-12 immunocytokine given intratumorally and the IL-15 immunocytokine given peritumorally, as described in the text. p, Overall survival of the mice shown in o. q, Weight of mice (n = 5/group) inoculated with 106 MC38 tumor cells and simultaneously treated with 4 µg IL-12 and 20 µg of IL-15 intratumorally on days marked with dotted lines and arrows. “x” denotes euthanasia due to poor body condition or weight-related criteria. Shown are mean ± s.d. from stated replicates. P values were determined by two-sided t-test, log-rank (Mantel-Cox), or two-way ANOVA followed by Tukey’s multiple comparison test. Exact P values are denoted in the figure; “ns” = not significant (P > 0.05).
