Fc-engineered antibodies with enhanced fc-effector function for the treatment of b-cell malignancies

Hilma J. van der Horst*, Inger S. Nijhof, Tuna Mutis, Martine E. D. Chamuleau

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

Monoclonal antibody (mAb) therapy has rapidly changed the field of cancer therapy. In 1997, the CD20-targeting mAb rituximab was the first mAb to be approved by the U.S. Food and Drug Administration (FDA) for treatment of cancer. Within two decades, dozens of mAbs entered the clinic for treatment of several hematological cancers and solid tumors, and numerous more are under clinical investigation. The success of mAbs as cancer therapeutics lies in their ability to induce various cytotoxic machineries against specific targets. These cytotoxic machineries include antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC), which are all mediated via the fragment crystallizable (Fc) domain of mAbs. In this review article, we will outline the novel approaches of engineering these Fc domains of mAbs to enhance their Fc-effector function and thereby their anti-tumor potency, with specific focus to summarize their (pre-) clinical status for the treatment of B-cell malignancies, including chronic lymphocytic leukemia (CLL), B-cell non-Hodgkin lymphoma (B-NHL), and multiple myeloma (MM).
Original languageEnglish
Article number3041
Pages (from-to)1-24
Number of pages24
JournalCancers
Volume12
Issue number10
DOIs
Publication statusPublished - 1 Oct 2020

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