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  • Poster presentation
  • Open Access

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

  • 1,
  • 2,
  • 3,
  • 3,
  • 1,
  • 1,
  • 4,
  • 3,
  • 2,
  • 1,
  • 5,
  • 2 and
  • 1
Journal for ImmunoTherapy of Cancer20142 (Suppl 3) :P95

https://doi.org/10.1186/2051-1426-2-S3-P95

  • Published:

Keywords

  • 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

(1)
Center for Applied Medical Research, Pamplona, Spain
(2)
Radboud University Nijmegen, Nijmegen, Netherlands
(3)
CIMA, University of Navarra, Pamplona, Spain
(4)
NIH - National Cancer Institute, Bethesda, MD, USA
(5)
Yale University, New Haven, CT, USA

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