COMBINATION ADOPTIVE IMMUNE CELL AND ANTI-CD47 THERAPY AND RELATED COMPOSITIONS

• Main Authors: YAMADA-HUNTER, Sean, MACKALL, Crystal, MCINTOSH, Brianna, COCHRAN, Jennifer R, THERUVATH, Johanna
• Format: Patent
• Language: English; French
• Published: 02.08.2024
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

Provided are nucleic acids encoding CD47 polypeptides. In some embodiments, the nucleic acids encode a CD47 polypeptide comprising a mutant CD47 Ig-like domain that reduces binding of a therapeutic anti-CD47 binding agent to the CD47 polypeptide as compared to binding of the therapeutic anti-CD47 binding agent to a wild-type CD47 polypeptide, and where the CD47 polypeptide retains binding to SIRPɑ. In certain embodiments, the mutant CD47 Ig-like domain comprises a mutant BC loop. Therapeutic immune cells (e.g., CAR-T cells, etc.) comprising the nucleic acids and expressing the CD47 polypeptides on their surface are also provided, as are therapeutic methods comprising administering such cells to subjects receiving an anti-CD47 therapy, e.g., to treat cancer. L'invention concerne des acides nucléiques codant des polypeptides CD47. Dans certains modes de réalisation, les acides nucléiques codent un polypeptide CD47 comprenant un domaine de type Ig CD47 mutant qui réduit la liaison d'un agent de liaison anti-CD47 thérapeutique au polypeptide CD47 par comparaison avec la liaison de l'agent de liaison anti-CD47 thérapeutique à un polypeptide CD47 de type sauvage, et le polypeptide CD47 conservant la liaison à SIRPɑ. Dans certains modes de réalisation, le domaine de type Ig CD47 mutant comprend une boucle BC mutante. L'invention concerne des cellules immunitaires thérapeutiques (par exemple, des cellules CAR-T, etc.) comprenant les acides nucléiques et exprimant les polypeptides CD47 sur leur surface, ainsi que des méthodes thérapeutiques consistant à administrer de telles cellules à des sujets recevant une thérapie anti-CD47, par exemple, pour traiter le cancer.