Abstract 261: Nivolumab and urelumab enhance antitumor activity of human T lymphocytes engrafted in Rag2-/-IL2Rγnull immunodeficient mice

Abstract To evaluate the pharmacodynamics effects and antitumor activities of immunostimulatory mAb, we have developed a “humanized” murine model in which the receptors targeted by such mAbs become expressed. Human lymphocytes transferred into immunodeficient mice undergo activation and redistribute to organs with surface expression of hCD137 and hPD-1. Systemic lymphocyte infiltrations result in lethal xenograft-versus-host disease, which is aggravated when mice are given clinical-grade anti-hCD137 (urelumab) and anti-hPD-1 (nivolumab) mAbs. In mice engrafted with either a human colorectal carcinoma cell line (HT-29) and allogeneic human PBMCs or a primary gastric carcinoma and PBMCs from the patient, urelumab and nivolumab significantly slowed tumor growth (p<0.01). Increased activated human T lymphocytes producing IFN-ϒ and decreased human regulatory T lymphocytes in the xenografted tumors may explain such therapeutic activities. These mouse models permit surrogate analyses to test and make predictions on immunotherapy strategies encompassing immunostimulatory mAbs and their combinations. Citation Format: Miguel F. Sanmamed, Inmaculada Rodriguez, Carmen Oñate, Arantza Azpilikueta, Maria E. Rodriguez-Ruiz, Aizea Morales-Kastresana, Sara Labiano, Jose L. Perez-Gracia, Salvador Martín-Algarra, Carlos Alfaro, Kurt A. Schalper, Guillermo Mazzolini, Francesca Sarno, Manuel Hidalgo, Alan J. Korman, Maria Jure-Kunkel, Ignacio Melero. Nivolumab and urelumab enhance antitumor activity of human T lymphocytes engrafted in Rag2-/-IL2Rγnull immunodeficient mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 261. doi:10.1158/1538-7445.AM2015-261