Chimeric antigen receptors against axl or ror2 and methods of use thereof

A chimeric antigen receptor, antigen technology, applied in the direction of antibodies, chemical instruments and methods, NGF-receptor/TNF-receptor superfamily, etc.

Pending Publication Date: 2019-08-27
F1 ONCOLOGY INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

There are many challenges in creating such a conditionally active CAR

Method used

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  • Chimeric antigen receptors against axl or ror2 and methods of use thereof
  • Chimeric antigen receptors against axl or ror2 and methods of use thereof
  • Chimeric antigen receptors against axl or ror2 and methods of use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach 1

[0413] Embodiment 1. A chimeric antigen receptor (CAR) for binding Ax1 or Ror2 comprising:

[0414] a) a conditionally active antigen-specific targeting region (ATR) that exhibits increased binding to Axl or Ror2 at pH 6.7 compared to pH 7.4;

[0415] b) a transmembrane domain; and

[0416] c) Intracellular activation domain.

Embodiment approach A1

[0417] Embodiment A1. A chimeric antigen receptor (CAR) for binding Axl or Ror2 comprising:

[0418] a) A conditionally active antigen-specific targeting region (ASTR) that exhibits increased (i.e. greater) activity in the tumor microenvironment and / or in vitro tumor replacement assay conditions compared to the normal physiological environment, wherein the ASTR is associated with Axl or Ror2 binding;

[0419] b) a transmembrane domain; and

[0420] c) Intracellular activation domain.

Embodiment approach A2

[0421] Embodiment A2. Unless expressly stated otherwise, the CAR of any one of embodiments 1 or A1 or according to any other embodiment provided herein, wherein the ASTR is selected from the group consisting of an antibody, an antigen, a ligand, a receptor binding structure of a ligand domains, receptors, ligand-binding domains of receptors and affibodies.

[0422] Embodiment A3. Unless expressly stated otherwise, the CAR of embodiment A2, or any other embodiment provided herein, wherein the ASTR is an antibody fragment.

[0423] Embodiment A4. Unless expressly stated otherwise, Embodiment 1 or any of A1 to A3 or the CAR according to any other embodiment provided herein, wherein the conditionally active ASTR is relative to the corresponding ASTR in the tumor microenvironment and / or in vitro tumor substitution assay conditions Physiological conditions exhibiting increased binding to antigen, wherein the tumor microenvironment and / or in vitro tumor surrogate assay conditions ar...

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Abstract

The present disclosure provides chimeric antigen receptors that bind to Axl and Ror2, and conditionally active chimeric antigen receptors (CARs) that recognize Axl and Ror2. Furthermore, provided herein are nucleic acids encoding these CARs and methods of making and using the CARs, including methods of treating cancer, especially cancers that express Axl and / or Ror2, such as renal cell carcinoma.The present disclosure provides cells genetically modified to produce the CARs.

Description

[0001] Cross References to Related Applications [0002] This application claims U.S. Provisional Application No. 62 / 447,898 filed January 18, 2017, U.S. Provisional Application No. 62 / 467,059 filed March 3, 2017, and U.S. Provisional Application No. 62 / 530,193 in equity. These applications cited in this paragraph are hereby incorporated by reference in their entirety. [0003] sequence listing [0004] This application hereby incorporates by reference the electronic Sequence Listing material filed herewith. The material in the Electronic Sequence Listing is submitted as a text (.txt) file named "F1.002.WO.01_Seqlist.txt", created on 1 / 17 / 2018, with a file size of 126KB and incorporated herein by reference in its entirety . [0005] joint research agreement [0006] F1 Oncology, Inc. and BioAtla, LLC are parties to a joint research agreement relating to the subject matter disclosed herein. technical field [0007] The present disclosure relates to chimeric antigen recep...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28A61K39/395
CPCC07K16/2803C07K16/2863A61K2039/505C07K2317/622C07K2319/03C07K2319/33C07K14/7051A61P35/00A61K35/17C07K14/70517C07K14/70521C07K14/70578C07K14/71C07K2317/73C12N5/0636C12N5/0646
Inventor 格雷戈里·伊恩·弗罗斯特詹姆斯·约瑟夫·奥努弗
Owner F1 ONCOLOGY INC
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