NEW METHOD TO IMPROVE NK CELLS CYTOTOXICITY

• Main Authors: BAHRI, Meriem, LE DOUSSAL, Jean-Marc, FOUGERAY, Sophie, BIRKLE, Stéphane, MADURA, Emilie
• Format: Patent
• Language: English; French; German
• Published: 21.02.2024
• Subjects: CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

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.