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.
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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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