The human anti-CD30 antibody 5F11 shows in vitro and in vivo activity against malignant lymphoma.
CD30 is a promising target for antibody-based immunotherapy of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma. To overcome the limitations from currently available murine anti-CD30 monoclonal antibodies (mAbs), a new fully human anti-CD30 antibody was generated. Binding properties were evaluated by recombinant CD30 capture enzyme-linked immunosorbent assay (ELISA) and fluorescence-activated cell-sorter (FACS) flow cytometry. Activity of this new mAb was assessed in vitro using growth inhibition and antibody-dependent cellular cytotoxicity (ADCC) assays on several cell lines. In vivo activity was determined in a solid as well as in a disseminated xenografted model of HL in severe combined immunodeficiency (SCID) mice. The mAb 5F11 showed specific binding to CD30 (cluster A). The ADCC assays indicated dose-dependent lysis of L540 cells when 5F11 was combined with human effector cells. Upon cross-linking in vitro, 5F11 inhibited the growth of CD30-expressing cell lines. In vivo, treatment with 5F11 induced a marked growth delay or even a complete regression of established xenografted HL in SCID mice. In the disseminated HL model, a high proportion of 5F11-treated mice experienced long-term survival. The new human anti-CD30 monoclonal antibody 5F11 shows promise as a means of CD30-targeted immunotherapy of malignant lymphomas. Based on these results, a clinical phase 1 study in patients with refractory CD30+ lymphoma has been initiated.
Borchmann
Peter
P
Klinik I für Innere Medizin der Universität Köln, Joseph-Stelzmann Strasse 9, 50924 Cologne, Germany. peter.borchmann@uni-koeln.de
Treml
John F
JF
Hansen
Hinrich
H
Gottstein
Claudia
C
Schnell
Roland
R
Staak
Oliver
O
Zhang
Hui-fen
HF
Davis
Thomas
T
Keler
Tibor
T
Diehl
Volker
V
Graziano
Robert F
RF
Engert
Andreas
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000915:Antibody Affinity; D000951:Antigens, Neoplasm / Q000276:immunology; D002455:Cell Division; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D017730:Ki-1 Antigen / Q000276:immunology*; D008223:Lymphoma / Q000188:drug therapy* / Q000401:mortality; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D015996:Survival Rate; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D017730:Ki-1 Antigen