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  • Poster presentation
  • Open Access

Focusing and sustaining the antitumor CTL effector killer response by agonist anti-CD137 mAb

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Journal for ImmunoTherapy of Cancer20142 (Suppl 3) :P95

  • Published:


  • Melanoma
  • Effector Function
  • Adoptive Transfer
  • Tumor Rejection
  • Synergistic Combination

B16-derived OVA-expressing melanomas resist curative immunotherapy with either adoptive transfer of activated anti-OVA OT1 cytotoxic T lymphocytes (CTLs) or agonist anti-CD137 (4-1BB) mAb. However when acting in synergistic combination, these treatments consistently achieve tumor eradication. Tumor-infiltrating lymphocytes that accomplish tumor rejection exhibit enhanced effector function in both transferred OT-1 and endogenous CTLs. This is consistent with higher levels of expression of eomesodermin in CTLs and with confocal microscopy evidence for more efficacious tumor-cell killing. Combined immunotherapy of tumors monitored by intravital live-cell two-photon microscopy reveals persistence of the OT1 CTL-effector phenotype over prolonged periods of time. Anti-CD137 mAb delayed loss of function with focused and confined interaction kinetics of OT-1 CTL with target cells lasting up to ten days post-transfer. The synergy of adoptive T cell therapy and anti-CD137 mAb thus results from in-vivo enhancement of effector functions.

Authors’ Affiliations

Center for Applied Medical Research, Pamplona, Spain
Radboud University Nijmegen, Nijmegen, Netherlands
CIMA, University of Navarra, Pamplona, Spain
NIH - National Cancer Institute, Bethesda, MD, USA
Yale University, New Haven, CT, USA


© Bolaños-Mateo et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.