Effective therapy for a murine model of human anaplastic large-cell lymphoma with the anti-CD30 monoclonal antibody, HeFi-1, does not require activating Fc receptors.
CD30 is a member of the tumor necrosis factor receptor family. Overexpression of CD30 on some neoplasms versus its limited expression on normal tissues makes this receptor a promising target for antibody-based therapy. Anaplastic large-cell lymphoma (ALCL) represents a heterogeneous group of aggressive non-Hodgkin lymphomas characterized by the strong expression of CD30. We investigated the therapeutic efficacy of HeFi-1, a mouse IgG1 monoclonal antibody, which recognizes the ligand-binding site on CD30, and humanized anti-Tac antibody (daclizumab), which recognizes CD25, in a murine model of human ALCL. The ALCL model was established by intravenous injection of karpas299 cells into nonobese diabetic/severe combined immuno-deficient (SCID/NOD) wild-type or SCID/NOD Fc receptor common gamma chain-deficient (FcRgamma(-/-)) mice. HeFi-1, given at a dose of 100 microg weekly for 4 weeks, significantly prolonged survival of the ALCL-bearing SCID/NOD wild-type and SCID/NOD FcRgamma(-/-) mice (P < .01) as compared with the control groups. In vitro studies showed that HeFi-1 inhibited the proliferation of karpas299 cells, whereas daclizumab did not inhibit cell proliferation. We demonstrated that the expression of FcRgamma on polymorphonuclear leukocytes and monocytes was not required for HeFi-1-mediated tumor growth inhibition in vivo, although it was required for daclizumab.
Metabolism Branch, Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Meili
M
Zhang
Zhengsheng
Z
Yao
Zhuo
Z
Zhang
Kayhan
K
Garmestani
Carolyn K
CK
Goldman
Jeffrey V
JV
Ravetch
John
J
Janik
Martin W
MW
Brechbiel
Thomas A
TA
Waldmann
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D000077561:Daclizumab; D004195:Disease Models, Animal; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007167:Immunotherapy / Q000379:methods; D017730:Ki-1 Antigen / Q000276:immunology; D017728:Lymphoma, Large-Cell, Anaplastic / Q000188:drug therapy*; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011961:Receptors, Fc / Q000378:metabolism*; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D007074:Immunoglobulin G; D017730:Ki-1 Antigen; D011961:Receptors, Fc; D000077561:Daclizumab