1. Immunotherapeutic targeting of surfaceome heterogeneity in AML
- Author
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Marie-Eve Bordeleau, Éric Audemard, Arnaud Métois, Louis Theret, Véronique Lisi, Azer Farah, Jean-François Spinella, Jalila Chagraoui, Ossama Moujaber, Léo Aubert, Banafsheh Khakipoor, Laure Mallinger, Isabel Boivin, Nadine Mayotte, Azadeh Hajmirza, Éric Bonneil, François Béliveau, Sybille Pfammatter, Albert Feghaly, Geneviève Boucher, Patrick Gendron, Pierre Thibault, Frédéric Barabé, Sébastien Lemieux, Guillaume Richard-Carpentier, Josée Hébert, Vincent-Philippe Lavallée, Philippe P. Roux, and Guy Sauvageau
- Subjects
CP: Cancer ,Biology (General) ,QH301-705.5 - Abstract
Summary: Immunotherapy remains underexploited in acute myeloid leukemia (AML) compared to other hematological malignancies. Currently, gemtuzumab ozogamicin is the only therapeutic antibody approved for this disease. Here, to identify potential targets for immunotherapeutic intervention, we analyze the surface proteome of 100 genetically diverse primary human AML specimens for the identification of cell surface proteins and conduct single-cell transcriptome analyses on a subset of these specimens to assess antigen expression at the sub-population level. Through this comprehensive effort, we successfully identify numerous antigens and markers preferentially expressed by primitive AML cells. Many identified antigens are targeted by therapeutic antibodies currently under clinical evaluation for various cancer types, highlighting the potential therapeutic value of the approach. Importantly, this initiative uncovers AML heterogeneity at the surfaceome level, identifies several antigens and potential primitive cell markers characterizing AML subgroups, and positions immunotherapy as a promising approach to target AML subgroup specificities.
- Published
- 2024
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