Fc-Engineered Antibodies with Enhanced Fc-Effector Function for the Treatment of B-Cell Malignancies
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...
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2020-10-01
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doaj-47e75e862ee64cb083500bbf6792a4af2020-11-25T02:26:15ZengMDPI AGCancers2072-66942020-10-01123041304110.3390/cancers12103041Fc-Engineered Antibodies with Enhanced Fc-Effector Function for the Treatment of B-Cell MalignanciesHilma J. van der Horst0Inger S. Nijhof1Tuna Mutis2Martine E. D. Chamuleau3Department of Hematology, Cancer Center Amsterdam, Amsterdam UMC, VU Medical Center, 1081 HV Amsterdam, The NetherlandsDepartment of Hematology, Cancer Center Amsterdam, Amsterdam UMC, VU Medical Center, 1081 HV Amsterdam, The NetherlandsDepartment of Hematology, Cancer Center Amsterdam, Amsterdam UMC, VU Medical Center, 1081 HV Amsterdam, The NetherlandsDepartment of Hematology, Cancer Center Amsterdam, Amsterdam UMC, VU Medical Center, 1081 HV Amsterdam, The NetherlandsMonoclonal 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).https://www.mdpi.com/2072-6694/12/10/3041antibody therapyFc engineeringimmunotherapyB-cell malignanciesB-cell lymphomaB-CLL |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hilma J. van der Horst Inger S. Nijhof Tuna Mutis Martine E. D. Chamuleau |
spellingShingle |
Hilma J. van der Horst Inger S. Nijhof Tuna Mutis Martine E. D. Chamuleau Fc-Engineered Antibodies with Enhanced Fc-Effector Function for the Treatment of B-Cell Malignancies Cancers antibody therapy Fc engineering immunotherapy B-cell malignancies B-cell lymphoma B-CLL |
author_facet |
Hilma J. van der Horst Inger S. Nijhof Tuna Mutis Martine E. D. Chamuleau |
author_sort |
Hilma J. van der Horst |
title |
Fc-Engineered Antibodies with Enhanced Fc-Effector Function for the Treatment of B-Cell Malignancies |
title_short |
Fc-Engineered Antibodies with Enhanced Fc-Effector Function for the Treatment of B-Cell Malignancies |
title_full |
Fc-Engineered Antibodies with Enhanced Fc-Effector Function for the Treatment of B-Cell Malignancies |
title_fullStr |
Fc-Engineered Antibodies with Enhanced Fc-Effector Function for the Treatment of B-Cell Malignancies |
title_full_unstemmed |
Fc-Engineered Antibodies with Enhanced Fc-Effector Function for the Treatment of B-Cell Malignancies |
title_sort |
fc-engineered antibodies with enhanced fc-effector function for the treatment of b-cell malignancies |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2020-10-01 |
description |
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). |
topic |
antibody therapy Fc engineering immunotherapy B-cell malignancies B-cell lymphoma B-CLL |
url |
https://www.mdpi.com/2072-6694/12/10/3041 |
work_keys_str_mv |
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