公开(公告)号：US20240228659A1

公开(公告)日：2024-07-11

申请号：US18555459

申请日：2022-04-13

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  NANTES UNIVERSITÉ ,  OGD2 PHARMA

发明人： Stéphane BIRKLE ,  Meriem BAHRI ,  Sophie FOUGERAY ,  Jean-Marc LE DOUSSAL ,  Emilie MADURA

IPC分类号： C07K16/30 ,  A61K31/203 ,  A61K39/00 ,  A61K39/395 ,  A61P35/00 ,  C07K16/28

CPC分类号： C07K16/3084 ,  A61K31/203 ,  A61K39/39558 ,  A61P35/00 ,  C07K16/2827 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/732 ,  C07K2317/76

摘要： A combination of retinoic acid, an anti-O-acetylated disialoganglioside (OAcGD2) compound and an anti-PD1/PD-L1 compound for treating a cancer, particularly neuroblastoma, in a subject in need thereof. The inventors focused on immunotherapeutic strategies targeting OAcGD2, believing they could address critical neuropathic pain side effects associated with anti-GD2 mAb infusions. They reported mAb 8B6 targeting OAcGD2 displays antitumor activity in NB tumor models, with induction of ADCC similarly to anti-GD2 mAbs. From this, the inventors interrogated whether 13-cis-RA and retinoic acid generally, may augment anti-NB efficiency of mAb 8B6 therapy. They found cooperative interaction of 13-cis-RA and mAb 8B6 treatment in inhibiting the NB growth in vivo. However, this combination regimen also coordinates PD-1/PD-L1 upregulation, which hinders a long-term activation of NK cells and allows tumor cell to relapse. Importantly this counter therapeutic effect can be leveraged with PD1 blockade to improve the therapeutic response of the mAb 8B6+13-cis-RA regimen.

公开(公告)号：US20240190993A1

公开(公告)日：2024-06-13

申请号：US18555093

申请日：2022-04-13

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  OGD2 PHARMA ,  NANTES UNIVERSITÉ

发明人： Stéphane BIRKLE ,  Sarah VERMEULEN ,  Sophie FOUGERAY ,  Meriem BAHRI ,  Emilie MADURA ,  Jean-Marc LE DOUSSAL

IPC分类号： C07K16/30 ,  A61K31/203 ,  A61K39/00 ,  A61P35/00 ,  C07K14/55 ,  C07K16/28

CPC分类号： C07K16/3084 ,  A61K31/203 ,  A61P35/00 ,  C07K14/55 ,  C07K16/2803 ,  C07K16/2896 ,  A61K2039/507 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/565

摘要： 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.