title: Anti-CD137 monoclonal antibodies and adoptive T cell therapy: a perfect marriage?
abstract: CD137(4-1BB) costimulation and adoptive T cell therapy strongly synergize in terms of achieving maximal efficacy against experimental cancers. These costimulatory biological functions of CD137 have been exploited by means of introducing the CD137 signaling domain in clinically successful chimeric antigen receptors and to more efficiently expand T cells in culture. In addition, immunomagnetic sorting of CD137-positive T cells among tumor-infiltrating lymphocytes selects for the fittest antitumor T lymphocytes for subsequent cultures. In mouse models, co-infusion of both agonist antibodies and T cells attains marked synergistic effects that result from more focused and intense cytolytic activity visualized under in vivo microscopy and from more efficient entrance of T cells into the tumor through the vasculature. These several levels of dynamic interaction between adoptive T cell therapy and CD137 offer much opportunity to raise the efficacy of current cancer immunotherapies.
authors.affiliation: Department of Cell Biology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Bettina
authors.initials: B
authors.lastname: Weigelin
authors.affiliation: Centro de Investigación Médica Aplicada and Clinica Universidad de Navarra, University of Navarra, Avenida Pio XII, 55, 31008, Pamplona, Spain.
authors.forename: Elixabet
authors.initials: E
authors.lastname: Bolaños
authors.affiliation: Centro de Investigación Médica Aplicada and Clinica Universidad de Navarra, University of Navarra, Avenida Pio XII, 55, 31008, Pamplona, Spain.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Rodriguez-Ruiz
authors.affiliation: Centro de Investigación Médica Aplicada and Clinica Universidad de Navarra, University of Navarra, Avenida Pio XII, 55, 31008, Pamplona, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Martinez-Forero
authors.affiliation: Department of Cell Biology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Friedl
authors.affiliation: Centro de Investigación Médica Aplicada and Clinica Universidad de Navarra, University of Navarra, Avenida Pio XII, 55, 31008, Pamplona, Spain. imelero@unav.es.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Melero
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
keywords: Adoptive T cell transfer; CARTs; CD137 (4-1BB); Combined immunotherapy