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Cd83-binding chimeric antigen receptors

A technology of chimeric antigen receptors and antigens, applied in the direction of antibodies, antibody medical components, receptors/cell surface antigens/cell surface determinants, etc., can solve problems such as damage to patient immunity

Pending Publication Date: 2020-11-27
H LEE MOFFITT CANCER CENT & RES INST INC
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Current immunosuppressive measures control GVHD target cells but impair post-transplant immunity in patients

Method used

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  • Cd83-binding chimeric antigen receptors
  • Cd83-binding chimeric antigen receptors
  • Cd83-binding chimeric antigen receptors

Examples

Experimental program
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Effect test

example 1

[0306] Example 1: Novel human CD83 chimeric antigen receptor T cells prevent GVHD while maintaining donor antitumor immunity

[0307] introduce

[0308]Allo-HCT is a procedure performed with curative intent for high-risk hematologic malignancies and bone marrow failure syndromes. Worldwide, 30,000 patients receive allo-HCT annually, and despite standard pharmacological immunosuppression, 34%-89% of patients develop acute GVHD (Cutler C. et al., Blood 2014 124: 1372-1377; Pidala J. et al., Haematologica 2012 97:1882-1889). The current approach is the widespread use of inhibitory calcineurin inhibitors in combination with methotrexate, sirolimus, or mycophenolate mofetil to prevent GVHD. Despite known off-target impairment of beneficial GVL and limited tolerance induction (Zeiser R. et al., Blood [Blood] 2006 108:390-399), calcineurin inhibitors have been included in GVHD prevention and treatment for sustained For more than 30 years (PowlesR.L. et al., Lancet [Lancet] 1978 ...

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Abstract

Disclosed are compositions and methods for preventing graft versus host disease (GVHD) in subjects receiving donor cells. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed thatcan be used with adoptive cell transfer suppress alloreactive donor cells. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express theseCARs. Therefore, also disclosed are methods of suppressing alloreactive donor cells in a subject receiving transplant donor cells that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 634,435, filed February 23, 2018, and Application Serial No. 62 / 677,783, filed May 30, 2018, which are hereby incorporated by reference in their entirety . [0003] sequence listing [0004] This application contains a Sequence Listing created on February 21, 2019, filed electronically as an ASCII.txt file entitled "320803-2200 Sequence Listing_ST25." The contents of the Sequence Listing are incorporated herein in their entirety. Background technique [0005] Allogeneic hematopoietic cell transplantation (HCT) is an effective therapy for hematologic malignancies, but it is limited by acute graft-versus-host disease (GVHD). GVHD arises when donor T cells respond to genetically defined proteins on the host cell and is a key contributor to the high mortality associated with HCT. Dendritic cells (DC) play a major role in allogeneic T cell stimulat...

Claims

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Application Information

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IPC IPC(8): C07K16/28C07K16/30
CPCC07K16/2803A61K2039/505C07K2317/622C07K2319/03C07K2319/33C07K14/705C07K14/70503A61P37/06C07K2317/73A61K39/001A61K39/4615A61K2239/38A61K39/464411A61K2239/48A61K39/4631A61K39/4611C12N5/0636A61K39/4622C07K14/7051C07K2319/02C07K2317/565C12N2510/00A61K35/17
Inventor 马可·达维拉布莱恩·贝茨
Owner H LEE MOFFITT CANCER CENT & RES INST INC
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