Tcr-vbeta specific therapeutic molecules and uses thereof
OwnerMichael GIRARDI, Jingjing REN +2inventors
InventorsMichael GIRARDI, Jingjing REN, Xiaofeng LIAO, Julia Mae LEWIS
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Abstract
Provided are compositions and uses for binding a chimeric antigen receptor (CAR) or an antibody or antigen binding fragment to a Vβ region of a T cell receptor. Also provided are methods for treating a disease such as cancer or an autoimmune disease using Vβ region targeting molecules.
Claims120
A chimeric antigen receptor (CAR) comprising
- (i) an antigen binding molecule that specifically binds to a TCR Vβ region, (ii) an extracellular domain, (iii) a transmembrane domain, (iv) a costimulatory domain and (v) an activating domain,
- wherein the antigen binding molecule is a single chain variable fragment (scFv) comprising:
- (a) a variable heavy chain (VH) according to any one of SEQ ID NOs:
- 45-131 and 534-544, and/or
- (b) a variable light chain (VL) according to any one of SEQ ID NOs:
- 132-227 and 545-558.
An antibody or antigen-binding fragment thereof capable of specifically binding to a TCR Vβ region, comprising a heavy chain variable region (VH) having an amino acid sequence according to any of SEQ ID NOs:
- 228-295 and 559-569.
An antibody or antigen-binding fragment thereof capable of specifically binding to a TCR Vβ region, comprising a light chain variable region (VL) having an amino acid sequence according to any of SEQ ID NOs:
- 296-369 and 570-583.
A method for treating cancer in a subject in need thereof, the method comprising:
- administering to the subject a therapeutically effective amount of a T-cell composition comprising a CAR, wherein the CAR comprises (i) an antigen binding molecule that specifically binds to a TCR Vβ region, (ii) an extracellular domain, (iii) a transmembrane domain, (iv) a costimulatory domain and (v) an activating domain,
- wherein the antigen binding molecule is a single chain variable fragment (scFv) comprising:
- (a) a variable heavy chain according to any one of SEQ ID NOs:
- 45-131 and 534-544, and/or
- (b) a variable light chain according to any one of SEQ ID NOs:
- 132-227 and 545-558.
A method for treating cancer in a subject in need thereof, the method comprising:
- administering to the subject a therapeutically effective amount of a composition comprising an antibody or antigen-binding fragment thereof capable of specifically binding to a TCR Vβ region, comprising a (i) heavy chain variable region (VH) having an amino acid sequence according to any of SEQ ID NOs:
- 228-295 and 559-569, or
- (ii) a light chain variable region (VL) having an amino acid sequence according to any of SEQ ID NOs:
- 296-369 and 570-583.
A method for treating T-cell mediated diseases in a subject in need thereof, the method comprising:
- administering to the subject a therapeutically effective amount of a T-cell composition comprising a CAR, wherein the CAR comprises (i) an antigen binding molecule that specifically binds to a TCR Vβ region, (ii) an extracellular domain, (iii) a transmembrane domain, (iv) a costimulatory domain and (v) an activating domain,
- wherein the antigen binding molecule is a single chain variable fragment (scFv) comprising:
- (a) a variable heavy chain according to any one of SEQ ID NOs:
- 45-131 and 534-544, and/or
- (b) a variable light chain according to any one of SEQ ID NOs:
- 132-227 and 545-558.
A method for treating T-cell mediated diseases in a subject in need thereof, the method comprising:
- administering to the subject a therapeutically effective amount of a composition comprising an antibody or antigen-binding fragment thereof, capable of specifically binding to a TCR Vβ region, comprising a (i) heavy chain variable region (VH) having an amino acid sequence according to any of SEQ ID NOs:
- 228-295 and 559-569, and/or
- (ii) a light chain variable region (VL) having an amino acid sequence according to any of SEQ ID NOs:
- 296-369 and 570-583.
An adenoassociated virus (AAV) vector encoding a chimeric antigen receptor (CAR) comprising
- (i) an antigen binding molecule that specifically binds to a TCR Vβ region, (ii) an extracellular domain, (iii) a transmembrane domain, (iv) a costimulatory domain and (v) an activating domain,
- wherein the antigen binding molecule is a single chain variable fragment (scFv) comprising:
- (a) a variable heavy chain according to any one of SEQ ID NOs:
- 45-131 and 534-544, and/or
- (b) a variable light chain according to any one of SEQ ID NOs:
- 132-227 and 545-558.
Dependencies are inferred from the claim text.