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.
Zhang
Meili
M
Metabolism Branch, Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Yao
Zhengsheng
Z
Zhang
Zhuo
Z
Garmestani
Kayhan
K
Goldman
Carolyn K
CK
Ravetch
Jeffrey V
JV
Janik
John
J
Brechbiel
Martin W
MW
Waldmann
Thomas A
TA
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