Recombinant bispecific single chain antibody fragments induce Fc gamma-receptor-mediated elimination of CD30+ lymphoma cells.
Bispecific molecules (BSMs) facilitate the targeting of immune effector cells to tumor cells. Here we describe the construction and characterization of a recombinant BSM comprising two single chain fragments: H22(scFv), targeting the Fc gamma-receptor (CD64) on monocytes, and Ki4(scFv), targeting CD30 on Hodgkin lymphoma cells. A homologous, chemically-linked BSM has been described previously, but is heterogeneous and difficult to prepare. The recombinant version is easier to prepare and homogeneous, yet retains the antigen specificities and efficiently triggers CD64-related effector functions. The elimination of lymphoma cells was preferentially achieved by phagocytosis, not through the ADCC pathway additionally activated by the chemically-linked molecule.
Fraunhofer IME, Department of Pharmaceutical Product Development, Forckenbeckstr. 6, 52074 Aachen, Germany.
Katharina
K
Ranft
Theo
T
Thepen
Rainer
R
Fischer
Stefan
S
Barth
Michael
M
Stöcker
D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D002460:Cell Line; D003001:Cloning, Molecular; D006689:Hodgkin Disease / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000627:therapeutic use*; D017730:Ki-1 Antigen / Q000032:analysis / Q000276:immunology*; D010587:Phagocytosis; D017452:Receptors, IgG / Q000276:immunology*; D011994:Recombinant Proteins / Q000627:therapeutic use
D018033:Antibodies, Bispecific; D007128:Immunoglobulin Fragments; D017730:Ki-1 Antigen; D017452:Receptors, IgG; D011994:Recombinant Proteins; C055966:immunoglobulin Fv