Inmunomodulación mediada por CD137- Dr Ivan Forero
Agonist anti-CD137 (4-1BB) mAbs enhance CD8-mediated antitumor immunity. Agonist anti-human CD137 mAbs binding to four distinct epitopes on the CD137 glycoprotein costimulated T cell activation irrespective of the engaged epitope or its interference with CD137L binding. CD137 perturbation with all these agonist mAbs resulted in Ag and Ab internalization toward an endosomal vesicular compartment.. Efficient CD137 internalization required K63 polyubiquitination and endocytosed CD137-containing vesicles recruited TNFR-associated factor (TRAF) 2 and were decorated with K63 polyubiquitins. Consistent with a role for TRAF2 in CD137 signaling, transgenic mice functionally deficient in TRAF2 showed delayed immunotherapeutic activity of anti-CD137 mAbs. As a whole, these findings advance our knowledge of the mechanisms of action of anti-CD137 immunostimulatory mAbs such as those currently undergoing clinical trials in cancer patients.
T cell costimulation with anti-CD137 monoclonal antibodies is mediated by K63-polyubiquitin-dependent signals from endosomes.
Martinez-Forero I, Azpilikueta A, Bolaños-Mateo E, Nistal-Villan E, Palazon A, Teijeira A, Perez-Chacon G, Morales-Kastresana A, Murillo O, Jure-Kunkel M, Zapata JM, Melero I.
J Immunol. 2013 Jun 15;190(12):6694-70
- Bogota. Colombia 1978
- MD Universidad Nacional 2001
- PhD Universidad de Navarra 2009
- Postdoc Centro de Investigación Médica Aplicada 2009-2012
- Asesor Médico Bristol Myers Squibb 2013
- Profesor Asistente Universidad CES Colombia 2013-now
Place: CELLEX sala A11