PT  - JOURNAL ARTICLE
AU  - Nadal, Lisa
AU  - Peissert, Frederik
AU  - Elsayed, Abdullah
AU  - Weiss, Tobias
AU  - Look, Thomas
AU  - Weller, Michael
AU  - Piro, Geny
AU  - Carbone, Carmine
AU  - Tortora, Giampaolo
AU  - Matasci, Mattia
AU  - Favalli, Nicholas
AU  - Corbellari, Riccardo
AU  - Di Nitto, Cesare
AU  - Prodi, Eleonora
AU  - Libbra, Chiara
AU  - Galeazzi, Simone
AU  - Carotenuto, Claudiopietro
AU  - Halin, Cornelia
AU  - Puca, Emanuele
AU  - Neri, Dario
AU  - De Luca, Roberto
TI  - Generation and <em>in vivo</em> validation of an IL-12 fusion protein based on a novel anti-human FAP monoclonal antibody
AID  - 10.1136/jitc-2022-005282
DP  - 2022 Sep 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - e005282
VI  - 10
IP  - 9
4099  - http://jitc.bmj.com/content/10/9/e005282.short
4100  - http://jitc.bmj.com/content/10/9/e005282.full
SO  - J Immunother Cancer2022 Sep 01; 10
AB  - 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.