Granted Patent
B2
US 12,202,856 · App. 16/302,001 · Granted Jan 21, 2025
Tethered interleukin-2 to its receptor IL-2RBETA, a platform to enhance natural killer and regulatory T cell activity
Inventors:
Youssef Jounaidi (Boston, MA); Stuart Forman (Arlington, MA); Keith Miller (Lincoln, MA); Joseph F. Cotten (Northborough, MA)
Assignee:
The General Hospital Corporation
C07K14/55A61K39/4613A61K39/464406A61K39/464493C07K14/70521C07K14/7155C12N5/0646A61K9/0019A61K38/00A61K45/06A61K2239/31A61K2239/38A61K2239/47A61K2239/58C07K2319/33C12N2510/00
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Abstract
Fusion proteins comprising IL2 and IL2Rβ (e.g., CIRB), IL2, IL2Rβ and IL21R (e.g., CIRB21), and/or comprising IL2, IL2Rβ, and CD28 (e.g., CIRB28); natural killer (NK) cells that express the fusion proteins and methods of use thereof, e.g., to treat subjects with cancer; and regulatory T cells (T-regs) that express a fusion protein comprising IL2, IL2Rβ, and CD28 and methods of use thereof, e.g., to treat subjects with autoimmune disease or GVHD.
Claims (9)
1. A fusion protein comprising interleukin 2 (IL2) fused to the N-terminus of full-length interleukin 2 receptor beta (IL2Rβ) without a signal peptide, with an intervening linker comprising an extracellular domain of IL2Rα, and a cytoplasmic domain of interleukin 21 receptor (IL21R) at the C-terminus of IL2Rβ, optionally with an intervening linker therebetween.
2. The fusion protein of claim 1 , wherein:
the IL2 comprises SEQ ID NO:34, and/or
the IL2Rβ comprises amino acids 27-551 of SEQ ID NO:35.
3. The fusion protein of claim 1 , wherein the extracellular domain of IL2Rα comprises SEQ ID NO:28.
4. The fusion protein of claim 1 , wherein the cytoplasmic domain of IL21R comprises amino acids 254-538 of SEQ ID NO:36.
5. A nucleic acid encoding the fusion protein of claim 1 .
6. An expression vector comprising the nucleic acid of claim 5 , with one or more regulatory regions for expression of the fusion protein.
7. An isolated natural killer (NK) cell expressing a fusion protein of claim 1 , optionally wherein the NK cell also expresses CD16 and optionally NKP44, NKP46 and NKP30.
Assignments (2)
CONFIRMATORY LICENSE
Recorded Oct 12, 2022
From: MASSACHUSETTS GENERAL HOSPITAL
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 061387/0016 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 15, 2019
From: JOUNAIDI, YOUSSEF; FORMAN, STUART; MILLER, KEITH; COTTEN, JOSEPH F.
To: THE GENERAL HOSPITAL CORPORATION
Reel/Frame 048341/0202 →
Continuity (3)
Provisional Application
62471456
· Mar 15, 2017
Provisional Application
62338757
· May 19, 2016
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