Chimeric antigen receptor Anti-inflammatory cells and methods of use

Pending Publication Date: 2022-11-03
TRUSTEES OF DARTMOUTH COLLEGE THE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The chimeric immune cells effectively localize and activate at sites of inflammation, secreting anti-inflammatory proteins to inhibit immune cell activation and proliferation, thereby reducing inflammation and tissue damage, offering a targeted approach to treating autoimmune and inflammatory diseases.

Problems solved by technology

Although genetic modifications to stimulate the immune system are beneficial for battling infectious organisms and cancer, there also exists a set of devastating diseases that are caused by an over-zealous and unchecked immune response.

Method used

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  • Chimeric antigen receptor Anti-inflammatory cells and methods of use

Examples

Experimental program
Comparison scheme
Effect test

example 1

and Transduction of Treg Cells with a CAR Construct

[0080]A method to isolate and expand natural T-regs was developed using commonly available magnet sort systems (Liu, et al. (2006) J. Exp. Med. 203:1701-11). The isolated T cells were CD4+CD25+CD127− Foxp3+ and had a suppressive phenotype characterized by their ability to suppress CD41 T cell proliferation (FIG. 1). These cells were isolated, expanded, and transduced with a CAR construct composed of nucleic acids encoding a CAR protein fused to a truncated CD1.9 via T2A. Notably, Foxp3 expression was not lost after transduction (FIG. 2).

example 2

ion of a CAR and BCRF1

[0081]Nucleic acids encoding BCRF1 were inserted downstream of nucleic acids encoding a CAR and Foxp3 protein. Coding sequences for the CAR and Foxp3 were linked via CHYSEL peptide T2A and coding sequences for Foxp3 and BCRF1 were linked via P2A. The construct was transduced into an E86 packing cell line and BCRF1 was found to be actively secreted. ELISA analysis showed that high levels of human IL-10 were present in the E86 supernatants (˜49000 pg / mL) compared to untransduced control cells (˜30 pg / mL). It is expected that this construct will be viable in T cells and that BCRF1 will exert a suppressive affect on various lymphocytes.

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Abstract

A nucleic acid construct and an immune cell, which harbor nucleic acids encoding a CAR and nucleic acids encoding at least one anti-inflammatory or immunosuppressant protein and methods of using the same in treatment or amelioration of inflammation or immune-mediated autoimmunity are described.

Description

INTRODUCTION[0001]This application claims the benefit of priority of U.S. Provisional Application No. 62 / 233,517, filed Sep. 28, 2015, the content of which is incorporated herein by reference in its entirety.BACKGROUND[0002]Although genetic modifications to stimulate the immune system are beneficial for battling infectious organisms and cancer, there also exists a set of devastating diseases that are caused by an over-zealous and unchecked immune response. The targeting of self-antigens under normal physiologic conditions can cause a range of serious ailments including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and autoimmune encephalomyelitis. A relatively new set of autoimmune diseases, categorized as autoinflammatory diseases, have also been characterized including familial Mediterranean fever (FMF), neonatal onset multisystem inflammatory disease (NOMID), tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), defi...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): C12N5/0783A61K35/17A61K38/17C07K14/705C07K14/47C07K14/54C07K16/18
CPCC12N5/0637A61K35/17A61K38/178C07K14/7056C07K14/4702C07K14/5428C07K14/70503C07K16/18C12N2510/00A61K48/00A61P37/06A61P37/08A61K39/4621A61K39/464412A61K39/4631A61K39/46433A61K39/464452A61K39/4611C07K2317/622C07K2319/00
InventorSENTMAN, CHARLES L.ARELLANO, BENJAMINE H.
OwnerTRUSTEES OF DARTMOUTH COLLEGE THE