Recombinant bispecific single chain antibody fragments induce Fcγ-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 Fcγ-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.