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Focusing and sustaining the antitumor CTL effector killer response by agonist anti-CD137 mAb
  1. Elixabet Bolaños-Mateo1,
  2. Bettina Weigelin2,
  3. Alvaro Teijeira3,
  4. Ivan Martinez-Forero3,
  5. Sara Labiano1,
  6. Arantza Azpilicueta1,
  7. Aizea Morales-Kastresana4,
  8. Jose I Quetglas3,
  9. Esther Wagena2,
  10. Alfonso Rodriguez1,
  11. Lieping Chen5,
  12. Peter Friedl2 and
  13. Ignacio Melero1
  1. Aff1 grid.5924.a0000000419370271Center for Applied Medical Research Pamplona Spain
  2. Aff2 grid.5590.90000000122931605Radboud University Nijmegen Nijmegen Netherlands
  3. Aff3 grid.5924.a0000000419370271CIMA, University of Navarra Pamplona Spain
  4. Aff4 grid.48336.3a0000000419368075NIH - National Cancer Institute Bethesda MD USA
  5. Aff5 grid.47100.320000000419368710Yale University New Haven CT USA

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Meeting abstracts

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.