Abstracts of the 29th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC)
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Focusing and sustaining the antitumor CTL effector killer response by agonist anti-CD137 mAb
Journal for ImmunoTherapy of Cancer volume 2, Article number: P95 (2014)
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.
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Bolaños-Mateo, E., Weigelin, B., Teijeira, A. et al. Focusing and sustaining the antitumor CTL effector killer response by agonist anti-CD137 mAb. j. immunotherapy cancer 2 (Suppl 3), P95 (2014). https://doi.org/10.1186/2051-1426-2-S3-P95
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DOI: https://doi.org/10.1186/2051-1426-2-S3-P95