Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Type: Journal article
Title: Fc gamma receptor is not required for in vivo processing of radio- and drug-conjugates of the dead tumor cell-targeting monoclonal antibody, APOMAB®
Author: Staudacher, A.H.
Liapis, V.
Wittwer, N.L.
Tieu, W.
Lam, H.C.
Leusen, J.
Brown, M.P.
Citation: Biomedicine and Pharmacotherapy, 2022; 151:113090-1-113090-10
Publisher: Elsevier BV
Issue Date: 2022
ISSN: 0753-3322
Statement of
Alexander H. Staudacher, Vasilios Liapis, Nicole L. Wittwer, William Tieu, Hiu Chun Lam, Jeanette Leusen, Michael P. Brown
Abstract: The Fc region of a monoclonal antibody (mAb) can play a crucial role in its biodistribution and therapeutic activity. The chimeric mAb, chDAB4 (APOMAB®), which binds to dead tumor cells after DNA-damaging anti- cancer treatment, has been studied pre-clinically in both diagnostic and therapeutic applications in cancer. Given that macrophages contribute to the tumor accumulation of chDAB4 and its potency as an antibody drug con- jugate in vivo, we next wanted to determine whether the Fc region of the chDAB4 mAb also contributed. We found that, regardless of prior labeling with chDAB4, dead EL4 lymphoma or Lewis Lung (LL2) tumor cells were phagocytosed equally by wild-type or Fcγ knock-down macrophage cell lines. A similar result was seen with bone marrow-derived macrophages from wild-type, Fcγ knock-out (KO) and NOTAM mice that express Fcγ but lack immunoreceptor tyrosine-based activation motif (ITAM) signaling. Among EL4 tumor-bearing wild-type, Fcγ KO or NOTAM mice, no differences were observed in post-chemotherapy uptake of 89Zr-labeled chDAB4. Similarly, no differences were observed between LL2 tumor-bearing wild-type and Fcγ KO mice in post-chemotherapy uptake of 89Zr-chDAB4. Also, the post-chemotherapy activity of a chDAB4-antibody drug conjugate (ADC) directed against LL2 tumors did not differ among tumor-bearing wild-type, Fcγ KO and NOTAM mice, nor did the proportions and characteristics of the LL2 tumor immune cell infiltrates differ significantly among these mice. In conclusion, Fc-FcγR interactions are not essential for the diagnostic or therapeutic applications of chDAB4 conjugates because the tumor-associated macrophages, which engulf the chDAB4-labelled dead cells, respond to endogenous ‘eat me’ signals rather than depend on functional FcγR expression for phagocytosis.
Keywords: NOTAM; FcγR; APOMAB; ChDAB4; Zirconium-89; PBD dimer
Rights: © 2022 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (
DOI: 10.1016/j.biopha.2022.113090
Grant ID:
Appears in Collections:Pharmacology publications

Files in This Item:
File Description SizeFormat 
hdl_135743.pdfPublished version1.87 MBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.