Focusing and sustaining the antitumor CTL effector killer response by agonist anti-CD137 mAb.
- Resource Type
- Article
- Authors
- Weigelin, Bettina; Bolaños, Elixabet; Teijeira, Alvaro; Martinez-Forero, Ivan; Labiano, Sara; Azpilikueta, Arantza; Morales-Kastresana, Aizea; Quetglas, José I.; Wagena, Esther; Sánchez-Paulete, Alfonso Rodríguez; Chen, Lieping; Friedl, Peter; Melero, Ignacio
- Source
- Proceedings of the National Academy of Sciences of the United States of America. 6/16/2015, Vol. 112 Issue 24, p7551-7556. 6p.
- Subject
- *CYTOTOXIC T cells
*THERAPEUTIC use of monoclonal antibodies
*MELANOMA immunotherapy
*TUMOR treatment
*APOPTOSIS
- Language
- ISSN
- 0027-8424
Cancer immunotherapy is undergoing significant progress due to recent clinical successes by refined adoptive T-cell transfer and immunostimulatory monoclonal Ab (mAbs). B16F10-derived OVAexpressing mouse melanomas resist curative immunotherapy with either adoptive transfer of activated anti-OVA OT1 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 functions in both transferred OT-1 and endogenous cytotoxic T lymphocytes (CTLs). This is consistent with higher levels of expression of eomesodermin in transferred and endogenous CTLs and with intravital live-cell two-photon microscopy evidence for more efficacious CTL-mediated tumor cell killing. Anti-CD137 mAb treatment resulted in prolonged intratumor persistence of the OT1 CTL-effector cells and improved function with focused and confined interaction kinetics of OT-1 CTL with target cells and increased apoptosis induction lasting up to six days postadoptive transfer. The synergy of adoptive T-cell therapy and agonist anti-CD137 mAb thus results from in vivo enhancement and sustainment of effector functions. [ABSTRACT FROM AUTHOR]