Journal
EMBO MOLECULAR MEDICINE
Volume 12, Issue 2, Pages -Publisher
WILEY
DOI: 10.15252/emmm.201911223
Keywords
cancer; interferons; neovasculature; targeted therapy; tumor necrosis factor
Categories
Funding
- UGent Methusalem
- ERC Advanced (CYRE) [340941]
- ERC Proof of Concept (AcTafactors) [680889]
- FWO-V [G009614N]
- LabEx MAbImprove
- Orionis Biosciences
- Institut Carnot CALYM
- Canceropole-Institut National du Cancer (INCa)
- European Research Council (ERC) [680889] Funding Source: European Research Council (ERC)
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Systemic toxicities have severely limited the clinical application of tumor necrosis factor (TNF) as an anticancer agent. Activity-on-Target cytokines (AcTakines) are a novel class of immunocytokines with improved therapeutic index. A TNF-based AcTakine targeted to CD13 enables selective activation of the tumor neovasculature without any detectable toxicity in vivo. Upregulation of adhesion markers supports enhanced T-cell infiltration leading to control or elimination of solid tumors by, respectively, CAR T cells or a combination therapy with CD8-targeted type I interferon AcTakine. Co-treatment with a CD13-targeted type II interferon AcTakine leads to very rapid destruction of the tumor neovasculature and complete regression of large, established tumors. As no tumor markers are needed, safe and efficacious elimination of a broad range of tumor types becomes feasible.
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