PMID- 37834445
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231024
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 19
DP  - 2023 Oct 8
TI  - Development of a Cytotoxic Antibody-Drug Conjugate Targeting Membrane 
      Immunoglobulin E-Positive Cells.
LID - 10.3390/ijms241914997 [doi]
LID - 14997
AB  - High numbers of membrane immunoglobulin E (IgE)-positive cells are characteristic 
      of allergic conditions, atopic dermatitis, or IgE myeloma. Antibodies targeting 
      the extracellular membrane-proximal domain of the membranous IgE-B-cell receptor 
      (BCR) fragment can be used for specific depletion of IgE-BCR-positive cells. In 
      this study, we derivatized such an antibody with a toxin and developed an 
      antibody-drug conjugate (ADC) that showed strong cytotoxicity for an IgE-positive 
      target cell line. Site-specific conjugation with 
      maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl-monomethyl-auristatin 
      E via a newly introduced single cysteine residue was used to prepare a compound 
      with a drug-antibody ratio of 2 and favorable biophysical properties. The 
      antibody was rapidly taken up by the target cells, showing almost complete 
      internalization after 4 h of treatment. Its cytotoxic effect was potentiated upon 
      cross-linking mediated by an anti-human IgG F(ab')(2) fragment. Because of its 
      fast internalization and strict target specificity, this antibody-drug conjugate 
      presents a valuable starting point for the further development of an anti-IgE 
      cell-depleting agent, operating by the combined action of receptor cross-linking 
      and toxin-mediated cytotoxicity.
FAU - Rodak, Aleksandra
AU  - Rodak A
AD  - Institute of Molecular Biotechnology, Department of Biotechnology, University of 
      Natural Resources and Life Sciences (BOKU), Muthgasse 18, 1190 Vienna, Austria.
FAU - Stadlbauer, Katharina
AU  - Stadlbauer K
AUID- ORCID: 0000-0002-0724-5874
AD  - Institute of Molecular Biotechnology, Department of Biotechnology, University of 
      Natural Resources and Life Sciences (BOKU), Muthgasse 18, 1190 Vienna, Austria.
FAU - Bobbili, Madhusudhan Reddy
AU  - Bobbili MR
AD  - Institute of Molecular Biotechnology, Department of Biotechnology, University of 
      Natural Resources and Life Sciences (BOKU), Muthgasse 18, 1190 Vienna, Austria.
AD  - Ludwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation 
      with AUVA, Donaueschingenstrasse 13, 1200 Vienna, Austria.
FAU - Smrzka, Oskar
AU  - Smrzka O
AD  - Ablevia Biotech GmbH, Maria Jacobi Gasse 1, 1030 Vienna, Austria.
FAU - Ruker, Florian
AU  - Ruker F
AUID- ORCID: 0000-0001-7639-2686
AD  - Institute of Molecular Biotechnology, Department of Biotechnology, University of 
      Natural Resources and Life Sciences (BOKU), Muthgasse 18, 1190 Vienna, Austria.
FAU - Wozniak Knopp, Gordana
AU  - Wozniak Knopp G
AUID- ORCID: 0000-0002-4069-070X
AD  - Institute of Molecular Biotechnology, Department of Biotechnology, University of 
      Natural Resources and Life Sciences (BOKU), Muthgasse 18, 1190 Vienna, Austria.
LA  - eng
GR  - W1224/FWF Austrian Science Fund/
PT  - Journal Article
DEP - 20231008
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Immunoconjugates)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Antigen, B-Cell)
SB  - IM
MH  - *Immunoconjugates/pharmacology
MH  - Immunoglobulin E
MH  - *Antineoplastic Agents
MH  - Cell Line
MH  - Immunoglobulin G
MH  - Receptors, Antigen, B-Cell
PMC - PMC10573690
OTO - NOTNLM
OT  - IgE-multiple myeloma
OT  - anti-IgE antibody
OT  - antibody-drug conjugate
OT  - extracellular membrane proximal domain
OT  - internalization
COIS- The authors declare no conflict of interest.
EDAT- 2023/10/14 10:44
MHDA- 2023/10/23 01:18
PMCR- 2023/10/08
CRDT- 2023/10/14 01:05
PHST- 2023/09/05 00:00 [received]
PHST- 2023/10/05 00:00 [revised]
PHST- 2023/10/07 00:00 [accepted]
PHST- 2023/10/23 01:18 [medline]
PHST- 2023/10/14 10:44 [pubmed]
PHST- 2023/10/14 01:05 [entrez]
PHST- 2023/10/08 00:00 [pmc-release]
AID - ijms241914997 [pii]
AID - ijms-24-14997 [pii]
AID - 10.3390/ijms241914997 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Oct 8;24(19):14997. doi: 10.3390/ijms241914997.