Immunodepletion of MDSC by AMV564, a novel bivalent, bispecific CD33/CD3 T cell engager, ex vivo in MDS and melanoma

Mol Ther. 2022 Jun 1;30(6):2315-2326. doi: 10.1016/j.ymthe.2022.02.005. Epub 2022 Feb 9.


We have reported previously that CD33hi myeloid-derived suppressor cells (MDSCs) play a direct role in the pathogenesis of myelodysplastic syndromes (MDSs) and that their sustained activation contributes to hematopoietic and immune impairment, including modulation of PD1/PDL1. MDSCs can also limit the clinical activity of immune checkpoint inhibition in solid malignancies. We hypothesized that depletion of MDSCs may ameliorate resistance to checkpoint inhibitors and, hence, targeted them with AMV564 combined with anti-PD1 in MDS bone marrow (BM) mononuclear cells (MNCs) enhanced activation of cytotoxic T cells. AMV564 was active in vivo in a leukemia xenograft model when co-administered with healthy donor peripheral blood MNCs (PBMCs). Our findings provide a strong rationale for clinical investigation of AMV564 as a single agent or in combination with an anti-PD1 antibody and in particular for treatment of cancers resistant to checkpoint inhibitors.

Keywords: AMV564; CD33; MDS; MDSC; anti-PD1 combined treatment; melanoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Bispecific* / pharmacology
  • Antineoplastic Agents* / pharmacology
  • Humans
  • Melanoma* / drug therapy
  • Myelodysplastic Syndromes* / drug therapy
  • Myeloid-Derived Suppressor Cells*
  • Sialic Acid Binding Ig-like Lectin 3
  • T-Lymphocytes


  • Antibodies, Bispecific
  • Antineoplastic Agents
  • CD33 protein, human
  • Sialic Acid Binding Ig-like Lectin 3