New method to improve the anti-tumoral activity of macrophages

Abstract

The treatment of cancer and particularly the neuroblastoma, and a combination of an anti-O-acetylated disialoganglioside (OAcGD2) compound and an anti-SIRP-alpha/CD47 compound for treating a cancer in a subject in need thereof. The inventors hypothesized that CD47 expression would interfere with the contribution of macrophage to the therapeutic effect of anti-OAcGD2 mAbs. They found that NB cells up-regulate CD47 expression upon 8B6 mAb immunotherapy in vivo, allowing them to escape mAb 8B6-mediated ADP. Next, they demonstrate that an anti-SIRPα antibody that blocks the binding of CD47 to SIRPα enables macrophages to phagocyte anti-OAcGD2-opsonised CD47-expressing NB cells in vitro. As a result, the combination of CD47 blocking with the targeting of OAcGD2-positive NB cells greatly reduces tumor growth in syngeneic mice. These results suggest that the combination of anti-OAcGD2 mAbs with phagocytosis checkpoints inhibitors may represent a very effective regimen to achieve for lasting responses in a greater number of patients.

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