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

• Published in: Journal for immunotherapy of cancer 2014-11, Vol.2 (S3), p.P95-P95, Article P95
• Main Authors: Bolaños-Mateo, Elixabet, Weigelin, Bettina, Teijeira, Alvaro, Martinez-Forero, Ivan, Labiano, Sara, Azpilicueta, Arantza, Morales-Kastresana, Aizea, Quetglas, Jose I, Wagena, Esther, Rodriguez, Alfonso, Chen, Lieping, Friedl, Peter, Melero, Ignacio
• Format: Article
• Language: English
• Subjects: Immunotherapy; Microscopy; Poster Presentation
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1186/2051-1426-2-S3-P95

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.