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

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 organ...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2015-08, Vol.75 (15_Supplement), p.261-261
Main Authors: Sanmamed, Miguel F., Rodriguez, Inmaculada, Oñate, Carmen, Azpilikueta, Arantza, Rodriguez-Ruiz, Maria E., Morales-Kastresana, Aizea, Labiano, Sara, Perez-Gracia, Jose L., Martín-Algarra, Salvador, Alfaro, Carlos, Schalper, Kurt A., Mazzolini, Guillermo, Sarno, Francesca, Hidalgo, Manuel, Korman, Alan J., Jure-Kunkel, Maria, Melero, Ignacio
Format: Article
Language:English
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Summary: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
ISSN:0008-5472
1538-7445
DOI:10.1158/1538-7445.AM2015-261