title: Combination anti-CD137 and anti-CD40 antibody therapy in murine myc-driven hematological cancers.
abstract: In order to stimulate antigen presentation and T cell activity against cancer, we treated three different tumor models in mice with the monoclonal antibodies anti-CD40 plus anti-CD137 (BiMab). In a subcutaneous transplantable MC38 colon cancer model, there was significant enhancement in the survival of mice following BiMab treatment. Anti-CD40 has shown considerable success against lymphoma in previous studies by other investigators, and we also showed in this study that, in a model of Eμ-Myc lymphoma, there was a statistically significant enhancement of survival of mice following BiMab treatment. Following the success of the BiMab treatment in the previous two models, we wished to determine if it would be successful in a mouse model of multiple myeloma. Firstly, we tested a transplantable model of disease in which multiple myeloma cells derived from Vk*MYC mice were injected intravenously. A minor proportion of anti-CD137 and BiMab treated mice experienced prolongation of life beyond 250 days. Then we tested the therapy in a spontaneously occurring multiple myeloma model, in Vk*MYC transgenic mice. The majority of mice treated survived longer than control mice, although statistical significance was not demonstrated.
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne 3002, Australia.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Westwood
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne 3002, Australia; Cancer Therapeutics Program, Gene Regulation Laboratory, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne 3002, Australia.
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Matthews
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne 3002, Australia; Cancer Therapeutics Program, Gene Regulation Laboratory, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne 3002, Australia.
authors.forename: Jake
authors.initials: J
authors.lastname: Shortt
authors.affiliation: Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne 3002, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Faulkner
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne 3002, Australia.
authors.forename: Hollie J
authors.initials: HJ
authors.lastname: Pegram
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne 3002, Australia.
authors.forename: Connie P M
authors.initials: CP
authors.lastname: Duong
authors.affiliation: Comprehensive Cancer Center, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Chesi
authors.affiliation: Comprehensive Cancer Center, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA.
authors.forename: P Leif
authors.initials: PL
authors.lastname: Bergsagel
authors.affiliation: Oncology Research Unit, Pfizer Inc., San Diego, CA 92121, USA.
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Sharp
authors.affiliation: Pfizer Corporation, New London CT 06320, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Huhn
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne 3002, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville 3010, Australia; Department of Immunology, Monash University, Prahran 3181, Australia.
authors.forename: Phillip K
authors.initials: PK
authors.lastname: Darcy
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne 3002, Australia; Cancer Therapeutics Program, Gene Regulation Laboratory, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne 3002, Australia.
authors.forename: Ricky W
authors.initials: RW
authors.lastname: Johnstone
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne 3002, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville 3010, Australia; Department of Immunology, Monash University, Prahran 3181, Australia. Electronic address: michael.kershaw@petermac.org.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Kershaw
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D019013:CD40 Antigens / Q000037:antagonists & inhibitors* / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D016259:Genes, myc; D007167:Immunotherapy / Q000379:methods; D008223:Lymphoma / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000628:therapy*; D014407:Tumor Cells, Cultured; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000906:Antibodies; D019013:CD40 Antigens; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
keywords: Anti-CD137; Anti-CD40; Eμ-Myc; Lymphoma; Multiple myeloma; Vk*myc