Data from IgA-Mediated Killing of Tumor Cells by Neutrophils Is Enhanced by CD47–SIRPα Checkpoint Inhibition

• DOI: 10.1158/2326-6066.c.6550411.v1
• Publication Date: 2023-04-04T19:39:11Z
• Authors: Louise W. Treffers; Toine ten Broeke; Thies Rösner; J.H. Marco Jansen; Michel van Houdt; Steffen Kahle; Karin Schornagel; Paul J.J.H. Verku...; Jan M. Prins; Katka Franke; Taco W. Kuijpers; Timo K. van den Berg; Thomas Valerius; Jeanette H.W. Leusen; Hanke L. Matlung
• Keywords: CD47; Cancer Immunotherapy; Immune checkpoint

<div>Abstract<p>Therapeutic monoclonal antibodies (mAb), directed toward either tumor antigens or inhibitory checkpoints on immune cells, are effective in cancer therapy. Increasing evidence suggests that the therapeutic efficacy of these antigen–targeting mAbs is mediated—at least partially—by myeloid effector which controlled by innate immune-checkpoint interaction between CD47 and SIRPα. We others have previously demonstrated inhibiting CD47–SIRPα interactions can substantially potentiate antibody-dependent cellular phagocytosis cytotoxicity cells IgG both <i>in vivo</i> vitro</i>. IgA superior killing neutrophils compared with same variable regions, but impact IgA-mediated has not been investigated. Here, we show checkpoint inhibition further enhances destruction antibody–opsonized human neutrophils. This was shown for multiple types against different antigens, i.e., HER2/neu EGFR. Consequently, combining EGFR SIRPα proved to be eradicating vivo</i>. In a syngeneic model, eradication predominantly mediated granulocytes, were actively recruited site blockade. conclude cell enhanced inhibition. These findings provide basis targeting combination improve their potential clinical patients.</p></div>