TY - JOUR T1 - Generation and <em>in vivo</em> validation of an IL-12 fusion protein based on a novel anti-human FAP monoclonal antibody JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2022-005282 VL - 10 IS - 9 SP - e005282 AU - Lisa Nadal AU - Frederik Peissert AU - Abdullah Elsayed AU - Tobias Weiss AU - Thomas Look AU - Michael Weller AU - Geny Piro AU - Carmine Carbone AU - Giampaolo Tortora AU - Mattia Matasci AU - Nicholas Favalli AU - Riccardo Corbellari AU - Cesare Di Nitto AU - Eleonora Prodi AU - Chiara Libbra AU - Simone Galeazzi AU - Claudiopietro Carotenuto AU - Cornelia Halin AU - Emanuele Puca AU - Dario Neri AU - Roberto De Luca Y1 - 2022/09/01 UR - http://jitc.bmj.com/content/10/9/e005282.abstract N2 - Background In this study, we describe the generation of a fully human monoclonal antibody (named ‘7NP2’) targeting human fibroblast activation protein (FAP), an antigen expressed in the microenvironment of different types of solid neoplasms.Methods 7NP2 was isolated from a synthetic antibody phage display library and was improved by one round of mutagenesis-based affinity maturation. The tumor recognition properties of the antibody were validated by immunofluorescence procedures performed on cancer biopsies from human patients. A fusion protein consisting of the 7NP2 antibody linked to interleukin (IL)-12 was generated and the anticancer activity of the murine surrogate product (named mIL12-7NP2) was evaluated in mouse models. Furthermore, the safety of the fully human product (named IL12-7NP2) was evaluated in Cynomolgus monkeys.Results Biodistribution analysis in tumor-bearing mice confirmed the ability of the product to selectively localize to solid tumors while sparing healthy organs. Encouraged by these results, therapy studies were conducted in vivo, showing a potent antitumor activity in immunocompetent and immunodeficient mouse models of cancer, both as single agent and in combination with immune checkpoint inhibitors. The fully human product was tolerated when administered to non-human primates.Conclusions The results obtained in this work provided a rationale for future clinical translation activities using IL12-7NP2.All data relevant to the study are included in the article or uploaded as supplementary information. ER -