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Antibody-mediated targeting of TNFR2 activates CD8+ T cells in mice and promotes antitumor immunity.
Tam, Eric M; Fulton, Ross B; Sampson, James F; Muda, Marco; Camblin, Adam; Richards, Jennifer; Koshkaryev, Alexander; Tang, Jian; Kurella, Vinodh; Jiao, Yang; Xu, Lihui; Zhang, Kathy; Kohli, Neeraj; Luus, Lia; Hutto, Elizabeth; Kumar, Sandeep; Lulo, James; Paragas, Violette; Wong, Christina; Suchy, James; Grabow, Stephanie; Dugast, Anne-Sophie; Zhang, Hong; Depis, Fabien; Feau, Sonia; Jakubowski, Aniela; Qiao, Wenlian; Craig, Galina; Razlog, Maja; Qiu, James; Zhou, Yu; Marks, James D; Croft, Michael; Drummond, Daryl C; Raue, Andreas.
Afiliación
  • Tam EM; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA. ertam604@gmail.com andreas.raue@me.com.
  • Fulton RB; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Sampson JF; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Muda M; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Camblin A; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Richards J; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Koshkaryev A; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Tang J; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Kurella V; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Jiao Y; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Xu L; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Zhang K; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Kohli N; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Luus L; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Hutto E; Histo-Scientific Research Laboratories, Mount Jackson, VA 22842, USA.
  • Kumar S; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Lulo J; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Paragas V; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Wong C; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Suchy J; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Grabow S; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Dugast AS; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Zhang H; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Depis F; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Feau S; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Jakubowski A; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Qiao W; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Craig G; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Razlog M; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Qiu J; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
  • Zhou Y; University of California at San Francisco, San Francisco, CA 94110, USA.
  • Marks JD; University of California at San Francisco, San Francisco, CA 94110, USA.
  • Croft M; La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Drummond DC; University of California San Diego, La Jolla, CA 92037, USA.
  • Raue A; Merrimack Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
Sci Transl Med ; 11(512)2019 10 02.
Article en En | MEDLINE | ID: mdl-31578241
Tumor necrosis factor receptor 2 (TNFR2) is the alternate receptor for TNF and can mediate both pro- and anti-inflammatory activities of T cells. Although TNFR2 has been linked to enhanced suppressive activity of regulatory T cells (Tregs) in autoimmune diseases, the viability of TNFR2 as a target for cancer immunotherapy has been underappreciated. Here, we show that new murine monoclonal anti-TNFR2 antibodies yield robust antitumor activity and durable protective memory in multiple mouse cancer cell line models. The antibodies mediate potent Fc-dependent T cell costimulation and do not result in significant depletion of Tregs Corresponding human agonistic monoclonal anti-TNFR2 antibodies were identified and also had antitumor effects in humanized mouse models. Anti-TNFR2 antibodies could be developed as a novel treatment option for patients with cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Receptores Tipo II del Factor de Necrosis Tumoral / Anticuerpos Monoclonales Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Receptores Tipo II del Factor de Necrosis Tumoral / Anticuerpos Monoclonales Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos