A novel C2 domain binding CD33xCD3 bispecific antibody with potent T-cell redirection activity against acute myeloid leukemia.

Blood Advances
Priyanka Nair-GuptaFrançois Gaudet

Abstract

CD33 is expressed in 90% of patients with acute myeloid leukemia (AML), and its extracellular portion consists of a V domain and a C2 domain. A recent study showed that a single nucleotide polymorphism (SNP), rs12459419 (C > T), results in the reduced expression of V domain-containing CD33 and limited efficacy of V domain-binding anti-CD33 antibodies. We developed JNJ-67571244, a novel human bispecific antibody capable of binding to the C2 domain of CD33 and to CD3, to induce T-cell recruitment and CD33+ tumor cell cytotoxicity independently of their SNP genotype status. JNJ-67571244 specifically binds to CD33-expressing target cells and induces cytotoxicity of CD33+ AML cell lines in vitro along with T-cell activation and cytokine release. JNJ-67571244 also exhibited statistically significant antitumor activity in vivo in established disseminated and subcutaneous mouse models of human AML. Furthermore, this antibody depletes CD33+ blasts in AML patient blood samples with concurrent T-cell activation. JNJ-67571244 also cross-reacts with cynomolgus monkey CD33 and CD3, and dosing of JNJ-67571244 in cynomolgus monkeys resulted in T-cell activation, transient cytokine release, and sustained reduction in CD33+ leukocyte populations...Continue Reading

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Citations

Jun 26, 2020·Expert Opinion on Biological Therapy·Roland B Walter
Jan 16, 2021·Advanced Healthcare Materials·Anthony BrouillardAshish A Kulkarni
Jan 21, 2021·British Journal of Cancer·Ajit SinghIqbal S Grewal
Dec 19, 2020·Cells·María Pia LenzaJune Ereño-Orbea
Dec 29, 2020·Future Oncology·Mohammed O GbadamosiJatinder K Lamba
Mar 24, 2021·Proceedings of the National Academy of Sciences of the United States of America·Dana L E VergoossenMaartje G Huijbers
Mar 25, 2021·Journal of Hematology & Oncology·Hongtao Liu
May 28, 2021·Biomarker Research·Shujie ZhouJinming Yu
May 27, 2021·Journal for Immunotherapy of Cancer·Sayed Shahabuddin HoseiniNai-Kong V Cheung
Jun 3, 2021·International Journal of Molecular Sciences·Mariam ElshiatyPetros Christopoulos

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