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1. WO2020194306 - GENETICALLY REPROGRAMMED TREGS EXPRESSING CARS

Publication Number WO/2020/194306
Publication Date 01.10.2020
International Application No. PCT/IL2020/050360
International Filing Date 26.03.2020
IPC
C12N 15/63 2006.01
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09Recombinant DNA-technology
63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
C07K 16/28 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
28against receptors, cell surface antigens or cell surface determinants
C07K 16/12 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
12against material from bacteria
C07K 14/705 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
14Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
435from animals; from humans
705Receptors; Cell surface antigens; Cell surface determinants
A61P 1/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
1Drugs for disorders of the alimentary tract or the digestive system
C12N 5/0783 2010.01
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
5Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
07Animal cells or tissues
071Vertebrate cells or tissues, e.g. human cells or tissues
078Cells from blood or from the immune system
0783T cells; NK cells; Progenitors of T or NK cells
Applicants
  • GAVISH-GALILEE BIO APPLICATIONS LTD. [IL]/[IL]
Inventors
  • GROSS, Gideon
  • WEINSTEIN-MAROM, Hadas
  • POZNER, Sarah
  • KRONER, Amit
Agents
  • SCHWARZ, Mikael
Priority Data
62/823,71126.03.2019US
62/898,47110.09.2019US
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) GENETICALLY REPROGRAMMED TREGS EXPRESSING CARS
(FR) TREGS GÉNÉTIQUEMENT REPROGRAMMÉS EXPRIMANT LES CAR
Abstract
(EN)
Nucleic acid molecules comprising a nucleotide sequence encoding an activating chimeric antigen receptor (aCARs) are provided, said aCARs comprising (i) an extracellular binding-domain specifically binding an antigen selected from an antigen of the commensal gut microflora and a self- cell surface antigen specific to the lamina propria (LP) or submucosa of the gastrointestinal tract; (ii) a transmembrane domain; (iii) an intracellular domain including at least one signal transduction element that activates and/or co- stimulates a T cell; and optionally (iv) a stalk region linking the extracellular domain and the transmembrane domain. Compositions and vectors comprising the nucleic acid molecules encoding the aCAR as well as methods for preparing regulatory T cells comprising the vectors and expressing the aCARs are further provided as are methods for treating or preventing a disease, disorder or condition manifested in excessive activity of the immune system in a subject, comprising administering to said subject the mammalian Treg expressing on its surface an aCAR. The regulatory T cells optionally express a membrane-bound homodimeric IL-10 conferring a stable Tr1 phenotype.
(FR)
L'invention concerne des molécules d'acide nucléique comprenant une séquence nucléotidique codant pour un récepteur chimérique à l'antigène d'activation (aCAR), lesdits aCAR comprenant (i) un domaine de liaison extracellulaire se liant spécifiquement à un antigène sélectionné à partir d'un antigène de la microflore intestinale commensale et un antigène de surface cellulaire spécifique de la lamina propria (LP) du sujet ou de sa sous-muqueuse du tractus gastro-intestinal; (ii) un domaine transmembranaire; (iii) un domaine intracellulaire comprenant au moins un élément de transduction de signal activant et/ou co-stimulant un lymphocyte T; et éventuellement (iv) une région de tige reliant le domaine extracellulaire et le domaine transmembranaire. L'invention concerne en outre des compositions et des vecteurs comprenant les molécules d'acide nucléique codant pour aCAR ainsi que des procédés de préparation de lymphocytes T régulateurs comprenant les vecteurs et exprimant les aCAR, ainsi que des procédés de traitement ou de prévention d'une maladie, un trouble ou un état se manifestant par une activité excessive du système immunitaire chez un sujet, comprenant l'administration audit sujet des Treg mammifères exprimant sur leur surface un aCAR. Les lymphocytes T régulateurs expriment facultativement une IL-10 homodimère liée à une membrane conférant un phénotype Tr1 stable.
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