Conditional activation of IL-12 through a Fibronectin-EDB dependent switch gate.

Josephine D Kahn¹, Kothai Parthiban², Peter Slavny², Aaron Arvey¹, Marc Presler³, Jamie Nosbisch³, Adrienne Rothschilds¹, Allan Capili¹, Teresa Barata⁴, Joana Martins⁴, Jiang Zhu¹, Robert Kamen¹, Robert Tepper¹, Ton N Schumacher^1,5, Lioudmila Tchistiakova¹, Divya Mathur¹

¹Third Rock Ventures, Boston, MA, USA.

²IONTAS, Cambridge, UK.

³Certara Inc., Radnor, PA, USA.

⁴FairJourney Biologics, Porto, Portugal.

⁵Division of Molecular Oncology & Immunology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

PubMed DOI

Abstract

Potent immune-activators, such as interleukin-12 (IL-12) have been challenging to develop for the treatment of solid tumors due to high systemic toxicity. To expand the therapeutic window achievable with IL-12, we engineered a novel and reversible antibody format, comprising a switch arm and targeting arm, that permits conditional activation of IL12 only in the presence of the pan-tumor matrix ant…

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