Vascular targeting of anti-CD40 antibodies and IL-2 into autochthonous tumors enhances immunotherapy in mice
J. Clin. Invest. Juliana Hamzah, et al. 118:1691 doi:10.1172/JCI33201 [
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Figure 4CD40 expression on tumor blood vessels. (
A) To display blood vessels, 27-week-old RIP1-Tag5 mice were i.v. injected with FITC-labelled tomato lectin. Tumors were harvested and stained with anti-CD40 antibodies. Equally strong CD40 signals were visible in tumor nodules of different sizes analyzed in RIP1-Tag5 mice at 23, 25, and 30 weeks of age (data not shown). (
B) CD40 expression is not detectable by immunohistochemistry in normal pancreatic tissue. Dotted lines delineate islet of Langerhans. (
C) CD40 expression on lectin-perfused tumor vessels from 27-week-old
CD40–/–→RIP1-Tag5 (
CD40–/–→RT5) mice and (
D) absence of CD40 expression on the vasculature of 27-week-old C3H→RIP1-Tag5×
CD40–/– mice displayed after anti-CD31 and anti-CD40 staining. Original magnification, ×40. Scale bar: 25 μm. (
E) Survival analyses of chimeric RIP1-Tag5 mice and (
F) chimeric RIP1-Tag5 mice after anti-CD40–RGR/IL-2–RGR combination treatment (
n = 8;
P = 0.004 and
P = 0.03 compared with chimeric untreated controls).