Emanuele Puca, Philipp Probst, Marco Stringhini, Patrizia Murer, Giovanni Pellegrini, Samuele Cazzamalli, Cornelia Hutmacher, Baptiste Gouyou, Sarah Wulhfard, Mattia Matasci, Alessandra Villa, Dario Neri
We describe the cloning and characterization of a novel fusion protein (termed L19-mIL12), consisting of murine interleukin-12 in single-chain format, sequentially fused to the L19 antibody in tandem diabody format. The fusion protein bound avidly to the cognate antigen (the alternatively-spliced EDB domain of fibronectin), retained the activity of the parental cytokine and was able to selectively localize to murine tumors in vivo, as shown by quantitative biodistribution analysis. L19-mIL12 exhibited a potent anti-tumor activity in immunocompetent mice bearing CT26 carcinomas and WEHI-164 sarcomas, which could be boosted by combination with check-point blockade, leading to durable cancer eradication...
August 2, 2019: International Journal of Cancer. Journal International du Cancer