title: Galiximab (anti-CD80)-induced growth inhibition and prolongation of survival in vivo of B-NHL tumor xenografts and potentiation by the combination with fludarabine.
abstract: Galiximab is a primatized monoclonal antibody that targets CD80 expressed on malignant B cells and is being studied in the clinic as a potential treatment for follicular NHL. We have recently reported that galiximab signals B-NHL cells in vitro and inhibits cell growth and sensitizes resistant tumor cells to apoptosis by chemotherapeutic drugs. This study was designed to validate the in vitro findings in in vivo in mice. Thus, we examined in vivo the antitumor activity of galiximab used alone and in combination with chemotherapeutic agents in SCID mice bearing human lymphoma xenografts. The in vivo antitumor effects of galiximab used alone and in combination with fludarabine or doxorubicin were determined in solid and disseminated human B-lymphoma tumors grown in SCID mice. Galiximab monotherapy in vivo demonstrated significant antitumor activity in a Raji lymphoma solid tumor model and in an SKW disseminated lymphoma tumor model. There was significant inhibition in tumor growth and prolongation of survival. In vitro, galiximab sensitized Raji cells to apoptosis by both fludarabine and doxorubicin. Tumor growth inhibition was significantly enhanced when the mice were treated with the combination of galiximab and fludarabine. These findings support the potential clinical application of galiximab in combination with chemotherapeutic drugs for the treatment of CD80-expressing hematological malignancies.
authors.affiliation: Cancer Therapeutics, Biogen Idec, San Diego, CA 92122, USA.
authors.forename: Kandasamy
authors.initials: K
authors.lastname: Hariharan
authors.forename: Peter
authors.initials: P
authors.lastname: Chu
authors.forename: Tracey
authors.initials: T
authors.lastname: Murphy
authors.forename: Dana
authors.initials: D
authors.lastname: Clanton
authors.forename: Lisa
authors.initials: L
authors.lastname: Berquist
authors.forename: Arturo
authors.initials: A
authors.lastname: Molina
authors.forename: Steffan N
authors.initials: SN
authors.lastname: Ho
authors.forename: Mario I
authors.initials: MI
authors.lastname: Vega
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bonavida
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D018122:B7-1 Antigen / Q000037:antagonists & inhibitors*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000627:therapeutic use; D004357:Drug Synergism; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018122:B7-1 Antigen; D004317:Doxorubicin; D014740:Vidarabine; C024352:fludarabine; C437823:galiximab