T cell engaging bispecific antibodies targeting CD33 IgV and IgC domains for the treatment of acute myeloid leukemia Journal Article

   


Authors: Hoseini, S. S.; Vadlamudi, M.; Espinosa-Cotton, M.; Tran, H.; Feng, Y.; Guo, H. F.; Xu, H.; Cheung, I.; Cheung, N. K. V.
Article Title: T cell engaging bispecific antibodies targeting CD33 IgV and IgC domains for the treatment of acute myeloid leukemia
Abstract: Background Acute myeloid leukemia (AML) remains one of the most challenging hematological malignancies. Despite progress in therapeutics, majority of patients succumb to this neoplasm. CD33 is a proven therapeutic target, given its expression on most AML cells. Almost all anti-CD33 antibodies target the membrane distal immunoglobulin V (IgV) domain of the CD33 extracellular domain. Methods In this manuscript, we present data on three bispecific antibodies (BsAbs) against the CD33 IgV and membrane proximal immunoglobulin C (IgC) domains. We use in vitro binding and cytotoxicity assays to show the effect of these BsAbs on AML cell lines. We also use immunodeficient mice-bearing leukemias from cell lines and patient-derived xenografts to show the effect of these BsAbs in vivo. Results In vitro, the IgV-targeting BsAb had higher binding to AML cell lines using flow cytometry and delivered more potent cytotoxicity in T-cell-dependent cytotoxicity assays; importantly, the IgC domain-targeting outperformed the IgV domain-targeting BsAb in medullary and extramedullary leukemia animal models. Conclusions These data support further clinical development of this BsAb for first-in-human phase I clinical trial. © 2021 BMJ Publishing Group. All rights reserved.
Keywords: neoplasm; immunotherapy; antigens; antibodies
Journal Title: Journal for ImmunoTherapy of Cancer
Volume: 9
Issue: 5
ISSN: 2051-1426
Publisher: Biomed Central Ltd  
Date Published: 2021-05-01
Start Page: e002509
Language: English
DOI: 10.1136/jitc-2021-002509
PUBMED: 34035113
PROVIDER: scopus
PMCID: PMC8154967
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85106919369&doi=10.1136%2fjitc-2021-002509&partnerID=40&md5=0f84e66d67929558dd0ae9fa4fa69480
Notes: Article -- Export Date: 1 July 2021 -- Source: Scopus
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MSK Authors
  1. Nai-Kong Cheung
    648 Cheung
  2. Irene Y Cheung
    96 Cheung
  3. Hong Xu
    53 Xu
  4. Hong-Fen Guo
    73 Guo
  5. Yi Feng
    15 Feng
  6. Hoa Tran
    6 Tran
  7. Sayed Shahabuddin Hoseini
    13 Hoseini
  8. Madelyn Marie Espinosa Cotton
    16 Espinosa Cotton
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