| Literature DB >> 35150889 |
Pingyan Cheng1, Xianghong Chen1, Robert Dalton1, Alexandra Calescibetta1, Tina So1, Danielle Gilvary1, Grace Ward2, Victoria Smith3, Sterling Eckard3, Judith A Fox3, Jeanmarie Guenot3, Joseph Markowitz1, John L Cleveland4, Kenneth L Wright1, Alan F List5, Sheng Wei1, Erika A Eksioglu6.
Abstract
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.Entities:
Keywords: AMV564; CD33; MDS; MDSC; anti-PD1 combined treatment; melanoma
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Year: 2022 PMID： 35150889 PMCID： PMC9171150 DOI： 10.1016/j.ymthe.2022.02.005
Source DB: PubMed Journal: Mol Ther ISSN： 1525-0016 Impact factor: 12.910