Systematic evaluation of AML-associated antigens identifies anti-U5 SNRNP200 therapeutic antibodies for the treatment of acute myeloid leukemia Journal Article
| Authors: | Knorr, K.; Rahman, J.; Erickson, C.; Wang, E.; Monetti, M.; Li, Z.; Ortiz-Pacheco, J.; Jones, A.; Lu, S. X.; Stanley, R. F.; Baez, M.; Fox, N.; Castro, C.; Marino, A. E.; Jiang, C.; Penson, A.; Hogg, S. J.; Mi, X.; Nakajima, H.; Kunimoto, H.; Nishimura, K.; Inoue, D.; Greenbaum, B.; Knorr, D.; Ravetch, J.; Abdel-Wahab, O. |
| Article Title: | Systematic evaluation of AML-associated antigens identifies anti-U5 SNRNP200 therapeutic antibodies for the treatment of acute myeloid leukemia |
| Abstract: | Despite recent advances in the treatment of acute myeloid leukemia (AML), there has been limited success in targeting surface antigens in AML, in part due to shared expression across malignant and normal cells. Here, high-density immunophenotyping of AML coupled with proteogenomics identified unique expression of a variety of antigens, including the RNA helicase U5 snRNP200, on the surface of AML cells but not on normal hematopoietic precursors and skewed Fc receptor distribution in the AML immune microenvironment. Cell membrane localization of U5 snRNP200 was linked to surface expression of the Fcγ receptor IIIA (FcγIIIA, also known as CD32A) and correlated with expression of interferon-regulated immune response genes. Anti-U5 snRNP200 antibodies engaging activating Fcγ receptors were efficacious across immunocompetent AML models and were augmented by combination with azacitidine. These data provide a roadmap of AML-associated antigens with Fc receptor distribution in AML and highlight the potential for targeting the AML cell surface using Fc-optimized therapeutics. © 2023, The Author(s). |
| Keywords: | protein expression; gene sequence; human cell; nonhuman; flow cytometry; mass spectrometry; animal cell; gene expression; animal experiment; animal model; genetic variation; proteomics; gene activation; cell culture; western blotting; immunoprecipitation; cellular distribution; fc receptor; immunophenotyping; upregulation; bone marrow transplantation; small nuclear ribonucleoprotein; fluorescence activated cell sorting; transcriptome; azacitidine; tumor microenvironment; acute myeloid leukemia; cd32 antigen; sanger sequencing; human; article; hek293t cell line; k-562 cell line; crispr associated endonuclease cas9 |
| Journal Title: | Nature Cancer |
| Volume: | 4 |
| Issue: | 12 |
| ISSN: | 2662-1347 |
| Publisher: | Nature Research |
| Date Published: | 2023-12-01 |
| Start Page: | 1675 |
| End Page: | 1692 |
| Language: | English |
| DOI: | 10.1038/s43018-023-00656-2 |
| PUBMED: | 37872381 |
| PROVIDER: | scopus |
| PMCID: | PMC10733148 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Omar Abdel-Wahab -- Source: Scopus |
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