Recombinant bispecific single chain antibody fragments induce Fc gamma-receptor-mediated elimination of CD30+ lymphoma cells.

Cancer Lett

Fraunhofer IME, Department of Pharmaceutical Product Development, Forckenbeckstr. 6, 52074 Aachen, Germany.

Published: September 2009

AI Article Synopsis

  • Bispecific molecules (BSMs) are designed to connect immune cells to tumor cells for targeted therapy.
  • A new recombinant BSM was created using two specific fragments: one targets the Fc gamma-receptor on monocytes and the other targets CD30 on Hodgkin lymphoma cells.
  • This recombinant version is easier to produce and more uniform compared to a previous chemically-linked version, yet it effectively induces immune responses, particularly through phagocytosis to eliminate lymphoma cells rather than the ADCC pathway.

Article Abstract

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.

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Source
http://dx.doi.org/10.1016/j.canlet.2009.03.011DOI Listing

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