[go: up one dir, main page]

WO2026024468A1 - Modular linked chimeric antigen receptors - Google Patents

Modular linked chimeric antigen receptors

Info

Publication number
WO2026024468A1
WO2026024468A1 PCT/US2025/037092 US2025037092W WO2026024468A1 WO 2026024468 A1 WO2026024468 A1 WO 2026024468A1 US 2025037092 W US2025037092 W US 2025037092W WO 2026024468 A1 WO2026024468 A1 WO 2026024468A1
Authority
WO
WIPO (PCT)
Prior art keywords
chimeric antigen
antigen receptors
linked chimeric
modl
modular
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2025/037092
Other languages
French (fr)
Inventor
Paul Daniel Donohoue
Brian J. FRANCICA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Caribou Biosciences Inc
Original Assignee
Caribou Biosciences Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Caribou Biosciences Inc filed Critical Caribou Biosciences Inc
Publication of WO2026024468A1 publication Critical patent/WO2026024468A1/en
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/31—Chimeric antigen receptors [CAR]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4202—Receptors, cell surface antigens or cell surface determinants
    • A61K40/421—Immunoglobulin superfamily
    • A61K40/4211—CD19 or B4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4202—Receptors, cell surface antigens or cell surface determinants
    • A61K40/4214—Receptors for cytokines
    • A61K40/4215—Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR], CD30
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/7051—T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/10—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the structure of the chimeric antigen receptor [CAR]
    • A61K2239/23—On/off switch
    • A61K2239/24—Dimerizable CARs; CARs with adapter
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/73—Fusion polypeptide containing domain for protein-protein interaction containing coiled-coiled motif (leucine zippers)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/20—Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPR]

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Plant Pathology (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Mechanical Treatment Of Semiconductor (AREA)

Abstract

The invention comprises modular linked chimeric antigen receptors (MODL-CARs), cells expressing the MODL-CARs, compositions comprising the cells and methods of making and using the same, including methods of treatment with MODL-CAR expressing engineered cells.

Description

. - , , , .. . . . , . , , , __. , .. . , . ,,, ,--- , . , - - , ,. , .. , -- . - , . , . -. --- “ -” -. - . - , , , , . H L. , , . ,.., , . , H H,
, , . , . .. , , , , . - . , , , . . , . , , , . , , . , . ,-, - ,-- -. -- - , . . . , , , , , . , . , - -, -- , . - -- , . , - ,,,,,,, , , , , . , , , , , , , , ,,, , , ,, , , , , ,, , , , . .., , , , ,- , ,- , , , , , , , , , ,,- , , , . , , , , ,,.., , -, , , , , , , , ,,-, , , -, , , , , , , ,, , , , . ,.., -, . - , - . , HH - , , - , . - ,- 2, ,x n, , - - ,..,4 , . .,.., , , , , , , ,, ,,,,, , , , , -,-,- ,- , , , , , , ,-,-, -, - , -, ,- , ,, ,,, ,., .,,- , , , , , , , . , , ,,-,,, , , ,-, , , -, ,,-,-, , , , -,, , , , , , , , - -,. - - - .- -, - , - . . - -, - - - . , - , - - . . - - -, -. - - - , - , - - . . - -, -. , - - - - - , - - . - . , - , , -. - , . , -, ., , , ,, , , , , , , , . , , , , , , , ,-, ,- - , ,- , , , ,,-- , , , , . . , , , , , , - . , ,, , - , , -. - , . . ,,, , , -. , - , - , .- - , - - - , - . , , -, , , , , , , , ,, , , . , . --, . , , - , , . , - , --. ., ,, - - - .. ,, , . . , , , - - , , - . . ,,, , , , , , , , , - , ,, ,, - , , ,- , . -- . ,. ., -- 7 -- , ----. -- , ,, , , , , , , , , , , ,, ,, , ,, , ,, , ,, , , , , , , . , ,- , , , , , , , , , , , , , , , ,, , , , . , , , , , , , . , ,, , , , , , , , , . , , , , . , , , , . , ,, , , , , -, , . - ,, , , . , - ,, , . , , . , , ,,- , , ,, , ,-,-, , , ,. , , - - , , - - - - , , - , . . -, - , , , . , ,- - , , ,. - , - , - - , . - - - . .- , - . ,- - . -, -,-,,-,-.,-, -,,--,-,-, . - .- , -. , . , .- , - . , - . , . - - , , . . - ,. - - . - . - , . , ., " ,t. ..., .., " " " . ,- ., ,.., , . , . - - . , . . . . "." - . -. - - . . “ ” . . . “ ” .., ,n,. ,2., . ,.. ,., “- ” HH . - - -, , , ,-, ,-,-. - -, , , , , , -, , ,- , ,-,, , , -,.,-, , ,,,-,.,-, “ ” . ,. ,, , , , . , , ., “ ” “ ” . , , , “ . .., , ” “ ” ,.,- .., , , , , ' , , , ,, , .., ,- , , , , , ,, , , , , . , , . - “ ”. , . “ ” . , , , “. “” . ” , , - “ ” - . ,. , + + , , , . , . , . “ ” “ ”. , “ ,” “ . , ,” “ ” ,.., -, , . ,. ., , , -, - , .., , , . , - “ ” , , . , , “,,,” “ ” . “” - “ -” “ ” , - - . . “” “ ” “ ” “ ”. . . . “ ,.., . ” . “ ” “,” , . , . , . , , , , . .,, , . - .., - , -,., ,. , , , , . - .. , . - - - . - . , - . - - , - . , ,.,., , .., . , - - . - - - . . - -. - ., , . ,. - . - - . , , , -- - - , . ,, ,- - - . , H-L, -- - HH. , . - , - . -, ,. . -. - - . , - , , . , - - , . .. - - . . - . - - - . - - - . . - - -.., . ,, - , -L- ,..,H - , . . -- - , . . - - - . –,. . , - .--. .- .- - . ,, - .- -- -- . , -- - , - . , . , - . , , , , H2 H , .- , , “ ” - . - , . - - - , . L . . H, L H. , H L . . ,,L L L L. L , , L . , - .., . , - . . , H . , H .. , .., ... , , .,, , , . “ ”. , , “”, “”, ,. , , , . - .., . , . , . ,. , , , - . , - . , - , - - . , - – . , – – –- – - – . , - - . . - , . . . .., . , , . , - .., ., ,... .- -, , . ,., .,. ,..., -., . . ., , -, , .. - , - - . , -, , - . , - - – . – . , – – - – - . , - - – , “ ”.. . , ..,- ,- . ,.., ., , . , , ,---,--,----,,----,---,---,--,--,--- ., . ,---,---,--- . , , , - . , - . . , - , . , , . , - –- – – , - – – – . , . . - “ ” - . - - - - . - .., - . -- , .. .,,..., -, - - . -,., - ,, ., , . ,,,. , .., ,. “”. , , “”. . .-., ., . , , ., ., , ,....,,, – , ,. , ., -, ,. - . , -, , . , - . . , , , - – - – – . - – – – . –, – – . , - , , , . “ ” , - . - . , . - , , - ., - ,., .. . - , “,” - , . - . , - ,- . , , - , - - .., - , .,.,....,., , - . - .., . , .- . , . ,, ,,-- 2, ,H -. - , H . , , ,.., . . - . , - H. , L . L H , , , ,. , , , , , , , , , , , -,- , , , , , ,, ,-,,--,,-,--, , , -, ,- , ,, ,,, ,. , , , , , , , , .,- , ,-, , , -,,,,,,-,-,,, , , , , , , -, , , , -, . , , , , , - - . - . ,- ,.. - ,.. . , , - . . .. - - , , - . ., ,- , . . ,. , - . .,. - . , - . . .. - .. , ., L H . , ,. . ,,, , ., ,,, . , - xn.. , .. .,, . .,, - ,.. . , . H ,, - L . - , .,, .. , - ’ , . - . ., - x .. .. , , - xn , - . .. , , . , - ,. - - . ,,,,, , , ,, , , , ,, , , , , , ,,, , , , , , , , , , , ,, , , . . , - -. , . . - , ., , ,,, , ,,- , ,, , ,- ,- , , , , , , , , , , ,. ,-, - , , , ,, , -, , , , ,, , , ,, . , -, , , , , , , - , -..,, - . ,.. .. .- ,- .- , - . , -. , . . -, . , . . , , - . , . -. , .. . , , , , , - , . -, - . . , .., - , - . , , , , ,,,, . , ,, , , ,-, , . . , ’ ., “ ” .., - . ..,.. .,,. - , ., - . - -, , - - -- , , ,, . . - ..,, , , --- , . , .-,, , .. ,,- . , . .., -- . - .., - , , ’ - .’ , , . , -. , . -. -, ,,.., . , , . ,, -- ,- -, . - .., , , , ,- , , . , , - - - . , , . . , - , . , - , . , .., , ,.., , - .., -. . . , - ,,., -. -, - , , , - , ,-, - - , -- , , , , . ” - “. , , .., , , -. . . - , .. . ., -,- - , . , , , .. , , ,, , , , , , , , - , - ,,-- , , ,, -,,- , ,, - ,- , , , , .. , , - . . ,.-. , , , . , ..,,, -, , , , , ., ,, , , . , - , - , , . , . -. ., ,t. .. ,.,.., , ,. , , . , , . , , . ,. ,. ,. ,. , . ,.., . . , , ,.. , , . - . - . , - ..,. , , -. - . ..- . -, - - .. - . - .., . . - - - ,,, . - . . - . . -- . - - ,.., . . .., . - - , - , ., , -..,-,-,-,-,-,-,-,-,-,- , , ... ,-, -.,.., - ., , - . ,., --. . , - . . . . , , . .,,. , , ′ .. , ′, , , , , ,′ , . , - , ,′ , , , , , . . - . . , , . . - , .- . ′ , . . . . . -′ . - ,. , ,′ ,, , . . , . ′ ′ , . -.. ..,,. , , - .,. . , , . , , , , . , . , , , , , . , . , , . ,. . .. .. , , . ,- ,- -’, , ,- - , , - .,- . . , - , . - - ,. . , . ,. , , , . , . . , . ,. , . , .- , . , , . , , , , -. . , , “,” - . , . ’ ...,’- –’’- -’ , - . . ..,- ,’ , . . , - , . . ,.., ,.., -- . ,.., , .., ..., ,..,., . –. , , , , .,..., . .., , - , - . .,...,-. , , - ,., ., . , . –. - , - . , - . , - .. , - , ,., ...,–. - ,. , , , , , , . , , ,.., , . ., , , - , , , ,, . ,...-.,.,.. , , . . - , , ., , +,, . – , .,+, +,, +.,,.., .,. . , - . , - , . . + , ...,. ., . ----_, ,., ,, , . ,., , , , ., , -, - ,. , . , -. , - ,.., , -, ,.,,, . , , , . , , ,,,, ., , , -,-,--,,-,,-,, . , . , +. . ,- ,. , . - , . .. ,, --. -. , , -,- - . --- . - . , ,- . ,, . , . .., . , ,..., . . . , .., . , , . , , ,.., , - . + . ,- . ,, , . , , - -,-,.., - ,..,- -,..,.- . , - , ., , -- , ., -- . -- -- , - , -- . - - , , . . - . +-. - -, -, -, -, - , - ,- -, . . , - . ’ , + -, . -. - -, -, -, -, . , -, -, , . , . . -- - , - -, “ ” -. . , . - , , , - -- , ., -.,- , ,. -- . ,. . -. - , - , . , , -, , , , , , , , , , , , ,, . . ., - . , ., , .,. -– , ., - . ,., . , . - . . - , .... .,,. ,, . . . . . .,,, , . . . +-, + , , . ,- . ., , ., . + . + . , , ,- , ., - -- - , , . . . - - . , , - , , , . -, . - . , - . , , - - , - . .., . , . - - , . - , , , , , - - . , . . -. , -. - , , - -, , - . , - - -. - , . - , , - . , . - -- -- , - , , . . , - . -, -. - - - - . ,- . - . . ., , ..., ™ , - - -.., . , +- - .., . . , .., , - . - . - - . - , -- , - . -- . , -- . . -- . , - --- - , . , . . .., ™ , -- , . ---,-, -. . , -,-,-,-,-,.-, -- - . , . , - - - - . - , -- . , -- . -, - -- ,. ,-- . , , . -,- . . -- ,- . , . , -- -- - . , -- -- . - -- , ’ . , -+- ’ . , + - - - - - . . , - , -- - . -- , - -- - - . , , . , -- . - - - . - - , - - -- . , ,- ,, - , - . , , , . . , ,, , , , , , ,, , . . , , , , ,, , , ., , , , , , , , ,, ,- , , , ,, ,, ,, ,, , ,, ., , , , , , , , , , , . , , , . , , , , .,, , ., , , , , , ., ,, , , , , , ,. , , , , . , ,,, , , , . -- . . -- - , 7 ., 1 -- , . , -- . - . -- ., , , - . , , . , - , , . , , - , ,- . ,- , - , -. . , , ,, , ,, ,,,- , ,,,- -, . , . ,, , , , ,,- ,, , ,,,,-,-,, . - .. ,, - . ,, , , . . - ,. , , , , . , , , ,, -- ,, -- ,. , , . , . , ,.2, ,, , , . ,. 2 , - , ., , , ,. . , , , , ,, ,, , ,. ., . , , . ,, , , . ,, ,, ,, , , , , , . - - . .,- - , , , , . , . , . , . , . , - . . , . . , , , , , ., , , , , . ,, , , ,, ,, , . , , - , , , -,- , , -,-, . , -, -. -,, -, -. , , , , . -, . ,. - . ,- -- - ,- -. - . , - ---- ------. -- . , , . -- , ,.., - - . - - ...+ , - , -. .. , - .. , , - . , . - , , , , , ,,- . , , .,,-, - - , , ,-- . , . , ., , . , , , , - - -. - , , . , - , . , , - - , , .- , . - , , , , ,, - - - . , , ,. . . - . -. ™ - ,™ , . - -, - - , -- ,, . - - . . , , , . , , , . - . . - . . - , - . . . . , ,, .,. , , . , -. .. , , - ’ ’- ’ - . , “ . . ” . . ..,- , , . ’ . . . - . . ,.., . , , , . , , - , , , . . . . . TM- . , ,.. - . - - . , , ,.. ® .7 . . –, . TM . TM - TM, . .-- TM - ,. , - - -. - - 2. .. . - . - ’ ’- , , . - - -. ’ . , . . , TM , °, . , ° ,° -°.. , , , . - . , , . . ° ,° .°, °, .° . ,- . . , .°, °° °, - ° . ,,.,. - . . , , . , , .. , , - , ,. . . , , , , TM . - ™ , ,. , ,,., TM - , . - - ,.- . , , . . . . . . - . , .. . - . , . -. -. . , , -, . - . , , , - , , , ,, , , , , . , ,..,., ., , . . --__ --__ . - - “” “” . .- - - . , , . --- -- . “L” “H1” .L.H1
- ..,. . - , ,... . ,, , . - . __ __ __ __ . - - ..,., -L H - 4 - . . . - . -- , - . - . . . - - - -_ -_ -- - - -- _ _ - -- - - -- - - -- L H1 -- H1 L - . - - - __ __ -- _ _ _ _ - - . - - - - - - - - - - - - - - - - - - - . - - - - - - - - - - - - - - - - - - - - - - - - - -. - . - - , ,, - ,. . - -- -- - -- - -- -- -_- - - -- - - - - -- - - - - . . . , , - ,. , . ,,.., . , . , , -. , .,.., ... ., --. - , - , - , , - , ,, . . - , , , , . , ,. , , , , - -, - . , ’ ’ . ’ ’ . , - , ’ ’ - ..,’’ . . -. . . . - , . , ,. , . -- . , ,- . , .- - - , - - . -- . , -- - - . ™ . , - -- , .- ,,,,,,, - . = -. . - . -. - -- .-- -.., - .., , - ..,7. ,.., . . - - . - . . , - - , -, , - ,- -, , , --, , . . , -- -- -- - - - - - -- -- - -- . , . “” ,. “” , -- - - -- - - -- - - - - - - - - - - - - -- -- -- -- - - -- - - . , , . , .’ ’ ..,’’, . . .
. .. , , . . . .. . . . . . . . . . . . . . . . .. . . ... . . . . . . . . .. .. . . . .. .. . . . . . . . . . .. . . , , . , , . , .

Claims

. . - , , . - , . H . L.- ,, . - ., . H H. - ,
, , .. - , . . - , . , , .
. - . - -, . . ,, . - . ,, . - ., . - , . .. - ,, . -. , . , . - . , . - -, - -. - . -- , - -- . -. , . . - , . ... - ,, . - . ,, . - . ,,. . - - ., . - , - --. . - , - --. -. , ,,, , ,-,,,,,,,,,,,, , , , , , , , ,, , , , , , , , ,. , . .- , . - . , ,- ,,-,,, , ,-., , , , ,-, ,,,,, ,, ,, ,.. .- , ,, , , ,,-,, ,, , -, , , , , , , , -, ,. ,-, ,,, . . - . . , . - , . - - ,-.. - . ,, - - - , HH . ,- 2,.. -- , . , . x n,.. - , 4 .. -- ,, . .
. - , . , , , , , , , ,,, ,,,,, , , ,, -,-,- , , ,- ,-, - , , , -, , , -,,-, -, , , ., .,- , , , , , , ,,-,, , , , , , -, ,, , , ,-, , , -,-, , , , , -, , , , , , , , ,. .- , -.- -- . - - ., -. .- , .- -- ., -.- - , -. -- ., . .- , -.- -- . - - ,. -. .- , .- -- ,. - . - , - ..- -- ,. - - . -., ,- , . . . -. -, , , , , , ,. , , , , . ,, , , , , , , ,, , -, ,- , - , ,- , , - , , , ,- , ,. , .. , . , ,, ,, ,, --., . -. , . - . .. , , , ,. , , .. -. - - , . - ,. , - -- , - -. . , -, , , , , . , , , , , ,, ,. --,. . - , , , ,. , ., -. , -. . - , . - -. . . , - . , .., ., . ., , ,- -. , -. , , ,, , , , ,. , , ,. - , , , , , - , . , , - ,. . . , 7 . --. , . --.- - , - - - - -. -. , , , , , ,, , , , ,, , , , , , , , , , , , , , , , ,, ,, , ,,- ,, , , , , , . , , , , , , , , ,, , ,. , . , , , ,. , , , , . , ,, , , , . , ,. , , , , ,. , . . . , , , , ,. , , , , . - , , -. . , , -. , , . . , . , , ,, ,,-, , ,. ,,,,-,-, . , - , -, - - . - , , - , -- , . . , - , , , . ,- . , ,- , -- . , , ., . -, - . - - . - . . - , . . - , - - . ., . -,.-,-,-,-,,-,-,-,-, . -
. , -. - .-. ,. , . -. . , . ,. - . -. - , . . -- , , .
PCT/US2025/037092 2024-07-26 2025-07-10 Modular linked chimeric antigen receptors Pending WO2026024468A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202463676169P 2024-07-26 2024-07-26
US63/676,169 2024-07-26

Publications (1)

Publication Number Publication Date
WO2026024468A1 true WO2026024468A1 (en) 2026-01-29

Family

ID=96808908

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2025/037092 Pending WO2026024468A1 (en) 2024-07-26 2025-07-10 Modular linked chimeric antigen receptors

Country Status (1)

Country Link
WO (1) WO2026024468A1 (en)

Citations (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5482858A (en) 1987-05-21 1996-01-09 Creative Biomolecules, Inc. Polypeptide linkers for production of biosynthetic proteins
US5525491A (en) 1991-02-27 1996-06-11 Creative Biomolecules, Inc. Serine-rich peptide linkers
US6410319B1 (en) 1998-10-20 2002-06-25 City Of Hope CD20-specific redirected T cells and their use in cellular immunotherapy of CD20+ malignancies
US6849428B1 (en) 1997-03-05 2005-02-01 New England Biolabs, Inc. Intein-mediated protein ligation of expressed proteins
WO2011104382A1 (en) 2010-02-26 2011-09-01 Cellectis Use of endonucleases for inserting transgenes into safe harbor loci
WO2013098244A1 (en) 2011-12-30 2013-07-04 Wageningen Universiteit Modified cascade ribonucleoproteins and uses thereof
WO2014087010A1 (en) 2012-12-07 2014-06-12 Ablynx N.V. IMPROVED POLYPEPTIDES DIRECTED AGAINST IgE
US9260752B1 (en) 2013-03-14 2016-02-16 Caribou Biosciences, Inc. Compositions and methods of nucleic acid-targeting nucleic acids
US9650617B2 (en) 2015-01-28 2017-05-16 Pioneer Hi-Bred International. Inc. CRISPR hybrid DNA/RNA polynucleotides and methods of use
US10336810B2 (en) 2015-02-12 2019-07-02 University Health Network Chimeric antigen receptors, encoding nucleic acids and methods of use thereof
WO2019241452A1 (en) 2018-06-13 2019-12-19 Caribou Biosciences, Inc. Engineered cascade components and cascade complexes
WO2020150339A1 (en) 2019-01-16 2020-07-23 Caribou Biosciences, Inc. Humanized bcma antibody and bcma-car-t cells
WO2020206162A1 (en) 2019-04-03 2020-10-08 Regeneron Pharmaceuticals, Inc. Methods and compositions for insertion of antibody coding sequences into a safe harbor locus
US20200370067A1 (en) 2019-05-21 2020-11-26 University Of Washington Method to identify and validate genomic safe harbor sites for targeted genome engineering
WO2021050857A1 (en) 2019-09-13 2021-03-18 Memorial Sloan-Kettering Cancer Center Anti-cd371 antibodies and uses thereof
US11066657B2 (en) 2014-10-28 2021-07-20 Agrivida, Inc Methods and compositions for stabilizing trans-splicing intein modified proteases
WO2021152086A1 (en) 2020-01-30 2021-08-05 Bit Bio Limited Safe harbor loci
US11091541B2 (en) 2013-04-29 2021-08-17 Hoffmann-La Roche Inc. Human FcRn-binding modified antibodies and methods of use
US11104375B2 (en) 2019-04-02 2021-08-31 Denso Corporation Rotary electric machine control device and electric power steering apparatus using the same
WO2022086846A2 (en) 2020-10-19 2022-04-28 Caribou Biosciences, Inc. Dna-containing polynucleotides and guides for crispr type v systems, and methods of making and using the same
US20220348929A1 (en) 2019-12-09 2022-11-03 Caribou Biosciences, Inc. Crispr abasic restricted nucleotides and crispr accuracy via analogs
WO2023230447A1 (en) 2022-05-24 2023-11-30 Caribou Biosciences, Inc. Anti-ror1 antibody and ror1-targeting engineered cells
US20230416747A1 (en) 2020-10-26 2023-12-28 Arsenal Biosciences, Inc. Safe harbor loci
WO2024097763A1 (en) * 2022-11-01 2024-05-10 Memorial Sloan-Kettering Cancer Center Intein-based sorting system and modular chimeric polypeptides

Patent Citations (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5482858A (en) 1987-05-21 1996-01-09 Creative Biomolecules, Inc. Polypeptide linkers for production of biosynthetic proteins
US5525491A (en) 1991-02-27 1996-06-11 Creative Biomolecules, Inc. Serine-rich peptide linkers
US6849428B1 (en) 1997-03-05 2005-02-01 New England Biolabs, Inc. Intein-mediated protein ligation of expressed proteins
US6410319B1 (en) 1998-10-20 2002-06-25 City Of Hope CD20-specific redirected T cells and their use in cellular immunotherapy of CD20+ malignancies
WO2011104382A1 (en) 2010-02-26 2011-09-01 Cellectis Use of endonucleases for inserting transgenes into safe harbor loci
WO2013098244A1 (en) 2011-12-30 2013-07-04 Wageningen Universiteit Modified cascade ribonucleoproteins and uses thereof
WO2014087010A1 (en) 2012-12-07 2014-06-12 Ablynx N.V. IMPROVED POLYPEPTIDES DIRECTED AGAINST IgE
US9260752B1 (en) 2013-03-14 2016-02-16 Caribou Biosciences, Inc. Compositions and methods of nucleic acid-targeting nucleic acids
US11091541B2 (en) 2013-04-29 2021-08-17 Hoffmann-La Roche Inc. Human FcRn-binding modified antibodies and methods of use
US11066657B2 (en) 2014-10-28 2021-07-20 Agrivida, Inc Methods and compositions for stabilizing trans-splicing intein modified proteases
US9650617B2 (en) 2015-01-28 2017-05-16 Pioneer Hi-Bred International. Inc. CRISPR hybrid DNA/RNA polynucleotides and methods of use
US10336810B2 (en) 2015-02-12 2019-07-02 University Health Network Chimeric antigen receptors, encoding nucleic acids and methods of use thereof
WO2019241452A1 (en) 2018-06-13 2019-12-19 Caribou Biosciences, Inc. Engineered cascade components and cascade complexes
WO2020150339A1 (en) 2019-01-16 2020-07-23 Caribou Biosciences, Inc. Humanized bcma antibody and bcma-car-t cells
US11104375B2 (en) 2019-04-02 2021-08-31 Denso Corporation Rotary electric machine control device and electric power steering apparatus using the same
WO2020206162A1 (en) 2019-04-03 2020-10-08 Regeneron Pharmaceuticals, Inc. Methods and compositions for insertion of antibody coding sequences into a safe harbor locus
US20200370067A1 (en) 2019-05-21 2020-11-26 University Of Washington Method to identify and validate genomic safe harbor sites for targeted genome engineering
WO2021050857A1 (en) 2019-09-13 2021-03-18 Memorial Sloan-Kettering Cancer Center Anti-cd371 antibodies and uses thereof
US20220348929A1 (en) 2019-12-09 2022-11-03 Caribou Biosciences, Inc. Crispr abasic restricted nucleotides and crispr accuracy via analogs
WO2021152086A1 (en) 2020-01-30 2021-08-05 Bit Bio Limited Safe harbor loci
WO2022086846A2 (en) 2020-10-19 2022-04-28 Caribou Biosciences, Inc. Dna-containing polynucleotides and guides for crispr type v systems, and methods of making and using the same
US20230416747A1 (en) 2020-10-26 2023-12-28 Arsenal Biosciences, Inc. Safe harbor loci
WO2023230447A1 (en) 2022-05-24 2023-11-30 Caribou Biosciences, Inc. Anti-ror1 antibody and ror1-targeting engineered cells
WO2024097763A1 (en) * 2022-11-01 2024-05-10 Memorial Sloan-Kettering Cancer Center Intein-based sorting system and modular chimeric polypeptides

Non-Patent Citations (43)

* Cited by examiner, † Cited by third party
Title
"Antibodies: A Laboratory Manual", 2013, COLD SPRING HARBOR LAB. PRESS
ANDERSON, G.P. ET AL.: "Orthogonal synthetic zippers as protein scafolds", ACS OMEGA, vol. 3, 2018, pages 4810
ARMSTRONG, C. ET AL.: "SCORER 2.0: an algorithm for distinguishing parallel dimeric and trimeric coiled-coil sequences", BIOINFORMATICS, vol. 27, no. 14, 2011, pages 1908
BLUM, P.KAYSER, S.: "Chimeric Antigen receptor (CAR) T cell therapy in hematologic malignancies: clinical implications and limitations", CANCERS, vol. 16, no. 8, 2024, pages 1599
CHIDYAUSIKU, T.M. ET AL.: "De novo design of immunoglobulin-like domains", NATURE COMM, vol. 13, 2022, pages 5661
CHRISTIAN M. ET AL.: "Targeting DNA double-strand breaks with TAL effector nucleases", GENETICS, vol. 186, no. 2, 2010, pages 757 - 61
DENMAN ET AL.: "Membrane-Bound IL-21 Promotes Sustained Ex Vivo Proliferation of Human Natural Killer Cells", PLOS ONE, vol. 7, no. 1, 2012, pages 30264, XP055222111, DOI: 10.1371/journal.pone.0030264
EYQUEM J. ET AL.: "Targeting a CAR to the TRAC locus with CRISPRiCas9 enhances tumor rejection", NATURE, vol. 543, 2017, pages 113 - 117
GORNALUSSE ET AL.: "HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells", NAT. BIOTECHNOL., vol. 35, 2017, pages 765 - 772, XP093207611, DOI: 10.1038/nbt.3860
GUILINGER, J. P. ET AL.: "Fusion of catalytically inactive Cas9 to Fokl nuclease improves the specificity of genome modification", NATURE BIOTECHNOLOGY, vol. 32, no. 6, 2014, pages 577 - 582, XP055157221, DOI: 10.1038/nbt.2909
GUO CHANGJIANG ET AL: "The SpyCatcher-SpyTag interaction mediates tunable anti-tumor cytotoxicity of NK cells", MOLECULAR IMMUNOLOGY, PERGAMON, GB, vol. 165, 20 December 2023 (2023-12-20), pages 11 - 18, XP087448741, ISSN: 0161-5890, [retrieved on 20231220], DOI: 10.1016/J.MOLIMM.2023.12.001 *
GUO ET AL.: "CBLB ablation with CRISPR/Cas9 enhances cytotoxicity of human placental stem cell-derived NK cells for cancer immunotherapy", J IMMUNOTHER. OF CANCER, vol. 9, 2021, pages 001975
HERMANSON ET AL., HUMAN PLURIPOTENT STEM CELLS AS A RENEWABLE SOURCE OF NATURAL KILLER CELLS.
HIRABAYASHI KOICHI ET AL: "Dual-targeting CAR-T cells with optimal co-stimulation and metabolic fitness enhance antitumor activity and prevent escape in solid tumors", NATURE CANCER, vol. 2, no. 9, 23 September 2021 (2021-09-23), pages 904 - 918, XP093081941, Retrieved from the Internet <URL:https://www.nature.com/articles/s43018-021-00244-2> DOI: 10.1038/s43018-021-00244-2 *
IWAI ET AL.: "Highly efficient protein trans-splicing by a naturally split DiiaE, intein from Nostoc punctiforme", FEBS LETTERS, vol. 580, 2006, pages 1853
JACKSON ET AL.: "Sequential Single-Cell Transcriptional and Protein Marker Profiling Reveals TIGITas a Marker of CD19 CAR-T Cell Dysfunction in Patients with Non-Hodgkin Lymphoma", CANCER DISCOV, vol. 12, no. 8, 2022, pages 1886
KIM Y.G. ET AL.: "Hybrid restriction enzymes: zinc finger fusions to Fok 1cleavage domain,", PROC NATL ACAD SCI USA., vol. 93, no. 3, 1996, pages 1156 - 1160, XP002116423, DOI: 10.1073/pnas.93.3.1156
KLICHINSKY M ET AL.: "Human chimeric antigen receptor macrophages for cancer immunotherapy", NAT. BIOTECHNOL, vol. 38, no. 8, 2020, pages 947, XP055926928, DOI: 10.1038/s41587-020-0462-y
KOCHENDERFER ET AL., J. IMMUNOTHERAPY, vol. 32, 2009, pages 689 - 702
LAMETSCHWANDTNER ET AL.: "Cbl-b silenced human NK cells respond stronger to cytokine stimulation", J IMMUNOTHER. OF CANCER, vol. 3, 2015, XP021235292, DOI: 10.1186/2051-1426-3-S2-P230
LU ET AL.: "Cbl-b Is Upregulated and Plays a Negative Role in Activated Human NK Cells", J IMMUNOL, vol. 206, no. 4, 2021, pages 677 - 685, XP055914391, DOI: 10.4049/jimmunol.2000177
MAKAROVA ET AL.: "Evolution and classification of the CRISPR-Cas systems", NATURE REVIEWS MICROBIOLOGY, vol. 9, no. 6, June 2011 (2011-06-01), pages 467 - 477, XP055932744, DOI: 10.1038/nrmicro2577
MARCOS, E. ET AL.: "De novo design of a non-local β-sheet protein with high stability and accuracy", NATURE STRUCTURAL AND MOL. BIOL., vol. 25, 2018, pages 1028, XP036628335, DOI: 10.1038/s41594-018-0141-6
MAX JAN ET AL: "Reversible ON-and OFF-switch chimeric antigen receptors controlled by lenalidomide", SCI. TRANSL. MED, vol. 13, no. 6295, 6 January 2021 (2021-01-06), XP055982210 *
MONERA O.D. ET AL.: "Formation of parallel and antiparallel coiled-coils controlled by the relative positions of alanine residues in the hydrophobic core", J. BIO. CHEM., vol. 271, no. 8, 1996, pages 3995, XP002106709, DOI: 10.1074/jbc.271.8.3995
NAT. REV. MICROBIOL., vol. 18, 2020, pages 67 - 83
NAVABI ET AL.: "Designing and optimization of a single-chain fi-agiiient variable (scFv) antibody against IL2Rα (CD25): An in silico and in vitro study", IRAN J BASIC MED SCI, vol. 24, 2021, pages 1
NICHOLSON ET AL.: "Construction and characterization of a functional CD19-scpecific single chain Fv fragment for immunotherapy of B lineage leukaemia and lymphoma", MOL. IMMUNOL., vol. 34, 1997, pages 1157
NICHOLSON I.C. ET AL., MOLECULAR IMMUNOLOGY, vol. 34, no. 16-17, 1997, pages 1157
PANG ET AL.: "Activated Galectin-9/Tim3 promotes Treg and suppresses Th1 effector function in chronic lymphocytic leukemia", FASEB J, vol. 35, 2021, pages 21556
PAUSCH ET AL., SCIENCE, vol. 369, no. 6501, 2020, pages 333 - 337
PINOT ET AL.: "An expanded library of orthogonal split inteins enables modular multi-peptide assemblies", NAT COMMUN, vol. 11, 2020, pages 1529
ROWLEY, J. ET AL.: "Expression of IL-15RA or an IL-15 IL-15RA fusion on CD8 T cells modifies adoptively transferred T cell function in cis", EUR. J. IMMUNOL, vol. 39, 2009, pages 491, XP002679900, DOI: 10.1002/EJI.200838594
SHAPIRO ET AL.: "Lymphocyte activation gene 3: a novel therapeutic target in chronic lymphocytic leukemia", HAEMATOLOGICA, vol. 102, no. 5, 2017, pages 874, XP055553416, DOI: 10.3324/haematol.2016.148965
SINGH ET AL.: "Antigen-independent activation enhances the efficacy of 41BB co-stimulated CD22 CAR T cells", NAT. MED., vol. 27, no. 5, 2021, pages 842, XP037452985, DOI: 10.1038/s41591-021-01326-5
SMITH, J.W.: "Apheresis techniques and cellular immunomodulation", THER. APHER., vol. 1, 1997, pages 203 - 206
STEVENS ET AL.: "A promiscuous split intein with expanded protein engineering applications", PNAS, vol. 114, no. 32, 2017, pages 8538 - 8543, XP055661453, DOI: 10.1073/pnas.1701083114
STEVENS ET AL.: "Design of a Split Intein with Exceptional Protein Splicing Activity", J. AM. CHEM. SOC., vol. 138, no. 7, 2016, pages 2162 - 2165, XP055421171, DOI: 10.1021/jacs.5b13528
SWARTS ET AL., MOLECULAR CELL, vol. 66, 2017, pages 221 - 233
WANG ET AL., MOL. THERAPY - ONCOLYTICS, vol. 3, 2016, pages 16015
WOLL ET AL.: "Human embryonic stem cells differentiate into a homogeneous population of natural killer cells with potent in vivo antitumor activity", BLOOD, vol. 113, no. 24, 2016, pages 6094, XP055067678, DOI: 10.1182/blood-2008-06-165225
WOOD C.W.WOOLFSON, D. N.: "CCBuilder 2.0: Powerful and accessible coiled-coil modeling", PROTEIN SCI., vol. 27, no. 1, 2018, pages 103
YAMADA ET AL., CONSTRUCTION OF IGG-FAB2 BISPECIFIC ANTIBODY VIA INTEIN-MEDIATED PROTEIN TRANS-SPLICING REACTION, 2023

Similar Documents

Publication Publication Date Title
Shimada et al. Stability of heterochiral hybrid membrane made of bacterial sn-G3P lipids and archaeal sn-G1P lipids
Sant et al. Hybrid PGS–PCL microfibrous scaffolds with improved mechanical and biological properties
van den Dolder et al. Flow perfusion culture of marrow stromal osteoblasts in titanium fiber mesh
WO2026024468A1 (en) Modular linked chimeric antigen receptors
Truong et al. In situ fabrication of electrically conducting bacterial cellulose-polyaniline-titanium-dioxide composites with the immobilization of Shewanella xiamenensis and its application as bioanode in microbial fuel cell
CN1589987A (en) Method of producing solid wire for welding
Lligadas Renewable polyols for polyurethane synthesis via thiol‐ene/yne couplings of plant oils
Palaninathan et al. Bioactive bacterial cellulose sulfate electrospun nanofibers for tissue engineering applications
Rudd et al. A highly efficient tree structure for the biosynthesis of heparan sulfate accounts for the commonly observed disaccharides and suggests a mechanism for domain synthesis
ATE195304T1 (en) CHEMICAL GLASS FIBERS AND THEIR PRODUCTION AND USE
EA017675B1 (en) Heat-resistant sealant, endless sealing member using the same, and downhole unit furnished with endless sealing member
Faure et al. Holobiont: a conceptual framework to explore the eco-evolutionary and functional implications of host–microbiota interactions in all ecosystems
Mu et al. Engineering hydrogen bonding interaction and charge separation in bio-polymers for green lubrication
Palacio-Lopez et al. Experimental manipulation of pectin architecture in the cell wall of the unicellular charophyte, Penium margaritaceum
CN1217209C (en) Optical fibre and transmission path
Chong et al. Surface-induced formation and redox-dependent staining of outer membrane extensions in Shewanella oneidensis MR-1
CN102089426A (en) Cellular differentiation process and its use for blood vessel build-up
Kato et al. Clarifications and question specificity in synchronous social Q&A
Okpalugo et al. Human microvascular endothelial cellular interaction with atomic N‐doped DLC compared with Si‐doped DLC thin films
Pavia The Middle Pleistocene fossil avifauna from the “Elephas mnaidriensis Faunal Complex” of Sicily (Italy): preliminary results.
EP4635527A3 (en) Thymic constructs and uses thereof
CN109628351A (en) Composite deodurizing strain and its cultural method
Bahmed et al. Change of cell wall chitin content in amphotericin B resistant Kluyveromyces strains
JP7062579B2 (en) Surface protective agent composition and coated wire with terminals
Speijer How mitochondrial cristae illuminate the important role of oxygen during eukaryogenesis