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

被引：31

作者：

Cheng, Pingyan ^{[1
]}

Chen, Xianghong ^{[1
]}

Dalton, Robert ^{[1
]}

Calescibetta, Alexandra ^{[1
]}

So, Tina ^{[1
]}

Gilvary, Danielle ^{[1
]}

Ward, Grace ^{[2
]}

Smith, Victoria ^{[4
]}

Eckard, Sterling ^{[4
]}

Fox, Judith A. ^{[4
]}

Guenot, Jeanmarie ^{[4
]}

Markowitz, Joseph ^{[1
]}

Cleveland, John L. ^{[3
]}

Wright, Kenneth L. ^{[1
]}

List, Alan F. ^{[2
,5
]}

Wei, Sheng ^{[1
]}

Eksioglu, Erika A. ^{[1
]}

机构：

[1] H Lee Moffitt Canc Ctr & Res Inst, Dept Immunol, 12902 Magnolia Dr, Tampa, FL 33612 USA

[2] H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL 33612 USA

[3] H Lee Moffitt Canc Ctr & Res Inst, Dept Tumor Biol, Tampa, FL 33612 USA

[4] Amphivena Therapeut Inc, San Francisco, CA 94080 USA

[5] Precis BioSci, Durham, NC 27701 USA

来源：

MOLECULAR THERAPY | 2022年 / 30卷 / 06期

基金：

美国国家卫生研究院;

关键词：

ACUTE MYELOID-LEUKEMIA; MYELODYSPLASTIC SYNDROMES; SUPPRESSOR-CELLS; UP-REGULATION; EXPRESSION; IDENTIFICATION; PROLIFERATION; SURVIVAL; FUTURE; PD-1;

D O I：

10.1016/j.ymthe.2022.02.005

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

We have reported previously that CD33(hi) 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.

引用

页码：2315 / 2326

页数：12

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