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Citations to this article

Vascular targeting of anti-CD40 antibodies and IL-2 into autochthonous tumors enhances immunotherapy in mice
Juliana Hamzah, … , Günter J. Hämmerling, Ruth Ganss
Juliana Hamzah, … , Günter J. Hämmerling, Ruth Ganss
Published April 8, 2008
Citation Information: J Clin Invest. 2008;118(5):1691-1699. https://doi.org/10.1172/JCI33201.
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Research Article Oncology Article has an altmetric score of 6

Vascular targeting of anti-CD40 antibodies and IL-2 into autochthonous tumors enhances immunotherapy in mice

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Abstract

Current anticancer therapy is a delicate balance between elimination of malignant cells and harmful side effects for the host. In this study, we used a tumor-homing peptide to engineer anti-CD40 agonist antibodies and recombinant IL-2 such that they were selectively delivered into spontaneously arising tumors in a transgenic mouse model of islet cell carcinogenesis. Intravenous injection of these agents, either separately or together, led to accumulation in the vicinity of tumor neovessels without toxic side effects. Although both molecules are critical for adaptive immunity, the most profound effects were seen in endothelial cells. Combined, local anti-CD40 and IL-2 therapy reduced tumor vascularity and significantly delayed tumor growth in mice. Remarkably, tumor-bearing mice remained disease-free long-term when targeted anti-CD40 and IL-2 were combined with transfers of preactivated antitumor immune cells. In this therapeutic setting, triggering of CD40 on endothelial cells induced an inflammatory response of the vessel wall and facilitated effector cell accumulation in the tumor parenchyma while IL-2 promoted antigen-specific immune cell persistence. We believe this is a novel and highly effective anticancer approach, whereby tumor stroma is “conditioned” for enhanced immune cell entry and survival, facilitating immune-mediated tumor destruction and leading to a sustained antitumor response.

Authors

Juliana Hamzah, Delia Nelson, Gerd Moldenhauer, Bernd Arnold, Günter J. Hämmerling, Ruth Ganss

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Total citations by year

Year: 2024 2023 2022 2021 2020 2019 2018 2017 2014 2013 2012 2011 2010 Total
Citations: 1 1 1 1 2 2 2 3 4 2 5 3 1 28
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Citations to this article in year 2011 (3)

Title and authors Publication Year
Shifting the equilibrium in cancer immunoediting: from tumor tolerance to eradication
SA Quezada, KS Peggs, TR Simpson, JP Allison
Immunological Reviews 2011
The pharmacokinetics of Toll-like receptor agonists and the impact on the immune system
AL Engel, GE Holt, H Lu
Expert Review of Clinical Pharmacology 2011
Induction of potent anti-tumor responses while eliminating systemic side effects via liposome-anchored combinatorial immunotherapy
B Kwong, H Liu, DJ Irvine
Biomaterials 2011

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Referenced in 9 patents
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