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Chimeric antigen receptors and uses thereof

a technology of chimeric antigen and receptors, applied in the field of chimeric antigen receptors, can solve the problems of inability to isolate and expand t cell populations, distinctly heterogeneous, unpredictable and variable efficacy of this method, and achieve the effect of facilitating cell auto-stimulation

Pending Publication Date: 2021-02-11
BIOSCEPTRE PTY LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention is about modifying cells to have co-stimulatory receptors and their ligands, which allows the cells to auto-stimulate each other. This can be useful for research and treatment purposes.

Problems solved by technology

Whilst this approach has provided some initial promise in early investigations, there are many technical challenges associated with this approach.
The ability to isolate and expand T cell populations to clinically relevant numbers is technically challenging and the poorly controlled nature of the expansion results in a final T cell population that is distinctly heterogeneous, and may contain only a small number of cancer antigen-specific T cells.
As a result, the efficacy of this method is unpredictable and variable.
However, the efficacy of the CAR-transformed T cells led to significant hypercytokinemia, and ultimately death in some patients.

Method used

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  • Chimeric antigen receptors and uses thereof
  • Chimeric antigen receptors and uses thereof
  • Chimeric antigen receptors and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

example 1

Protocol for PEP2-2-3 binding peptide Chimeric Antigen Receptor (CAR) Design and Expression

[0207]An exemplified protocol detailing the process of designing and expressing an anti-non-functional (nf) P2X7 receptor CAR according to an embodiment of the present invention is detailed as follows.

Design of PEP2-2-3 (anti-nf P2x7) Chimeric Antigen Receptor

[0208]An anti-nfP2x7 chimeric antigen receptor (CAR) was designed according to the schematic illustrated in FIG. 1.

[0209]An antigen-recognition domain 1 of the CAR was generated which included the amino acid sequence of the PEP2-2-3 binding peptide (amino acid sequence set forth in SEQ ID NO: 10 and nucleotide sequence set forth in SEQ ID NO: 11). The PEP2-2-3 sequence was shown to have specific affinity for the dysfunctional P2X7 receptor expressed on cancer cells, such as prostate LNCap cells, without significant affinity for monocytes or lymphocytes.

[0210]A CD8a signalling peptide 2 (having the amino acid sequence set forth in SEQ ID N...

example 2

Design of Alternative Anti-nfP2X7 Chimeric Antigen Receptor

[0249]A further exemplified protocol detailing the process of designing, and expressing on a T cell, an anti-non-functional (nf) P2X7 receptor CAR, according to an embodiment of the present invention, is detailed below.

[0250]Anti-nfP2X7 CARs were designed utilising three anti-non-functioning P2X7 binding peptides. Specifically, CARs were designed to include antigen recognition domains with sequence homology to peptides PEP2-2-1-1, PEP2-472-2 or PEP2-2-12 (having the amino acid sequences set forth in SEQ ID NOs: 32, 33 and 34 respectively). These binding peptides have been shown to bind to the non-functional P2X7 receptor (Barden, J. A., Sluyter, R., Gu, B. J. & Wiley, J. S. 2003. Specific detection of non-functional human P2X(7) receptors in HEK293 cells and B-lymphocytes. FEBS Lett 538, 159-162).

[0251]The alignment of the above binding peptides to the heavy chain variable regions of antibodies that recognise non-functional ...

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Abstract

The present invention relates to chimeric antigen receptors (CARs) directed to cells expressing a dysfunctional or non-functional P2X purinoceptor 7 receptor. Further provided are methods of targeting neoplastic cells and tumours expressing a dysfunctional or non-functional P2X purinoceptor 7 receptor and methods of treating and preventing cancer is a subject.

Description

PRIORITY CLAIM[0001]This application is a continuation of U.S. application Ser. No. 15 / 759,046, filed Mar. 9, 2018, which is a national stage filing under 35 U.S.C. § 371 of PCT / AU2016 / 050851, filed Sep. 10, 2016, which claims priority from Australian provisional patent application number 2015903719, filed Sep. 11, 2015, the contents of each of which are incorporated herein by reference in their entirety.FIELD OF THE INVENTION[0002]The present invention relates to chimeric antigen receptors, T cells expressing chimeric antigen receptors and methods of using chimeric antigen receptors for the prevention and / or treatment of cancer.BACKGROUND OF THE INVENTION[0003]The immune system has highly evolved and specific mechanisms that protect us from a range of pathologies. Amongst these pathologies is the detection and elimination of unwanted pathogens such as bacterial infections, virally infected cells, and importantly, mutated cells that may cause malignant neoplasia (cancer). The abilit...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K35/17C07K14/725C07K14/705C07K14/735C07K14/715C12N5/0786C07K16/28
CPCA61K35/17C07K19/00C07K14/70521C07K14/70535C07K14/70578C07K14/715C12N5/0645C07K16/28C07K2317/622C07K2319/02C07K2319/03C07K2319/30C07K2319/33C07K2319/60C07K14/7051C12N5/0636C12N15/86A61K39/3955A61K47/6849A61K47/549A61P35/00A61P35/02C07K2317/24C07K2317/565C12N2510/00C12N2740/15043A61K39/4631A61K39/464402A61K39/4611C07K2319/00A61K35/00A61P1/00A61P1/02A61P1/04A61P1/18A61P11/00A61P13/08A61P13/10A61P13/12A61P15/00A61P17/00A61P25/00A61P35/04A61P5/14A61P7/00
Inventor COOMBS, JUSTIN T.BARRY, SIMON C.SADLON, TIMOTHY J.
Owner BIOSCEPTRE PTY LTD