Bispecific chimeric antigen receptors and encoding polynucleotides thereof
AssigneeSeattle Children's Hospital
InventorMichael Jensen
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Abstract
The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.
Claims28
A bispecific chimeric antigen receptor, comprising:
- a. at least two antigen-specific targeting regions;
- b. an extracellular spacer domain;
- c. a transmembrane domain;
- d. at least one co-stimulatory domain;
- and
- e. an intracellular signaling domain,
- wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and
- wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control.
A bispecific chimeric antigen receptor, comprising:
- a. at least two antigen-specific targeting regions;
- b. an extracellular spacer domain;
- c. a transmembrane domain;
- d. at least one co-stimulatory domain;
- and
- e. an intracellular signaling domain,
- wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and
- wherein the bispecific chimeric antigen receptor is co-expressed with truncated epidermal growth factor receptor (EGFRt).
A bispecific chimeric antigen receptor, comprising:
- a. at least two antigen-specific targeting regions;
- b. a CD8α hinge extracellular spacer domain;
- c. a CD8α transmembrane domain;
- d. a 4-1BB co-stimulatory domain;
- and
- e. a CD3 zeta intracellular signaling domain,
- wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen,
- wherein the bispecific chimeric antigen receptor is co-expressed with truncated epidermal growth factor receptor (EGFRt), and
- wherein the bispecific chimeric antigen receptor and EGFRt are linked via a T2A linker.
A bispecific chimeric antigen receptor-encoding polynucleotide, the polynucleotide comprising:
- a. a nucleic acid encoding (i) at least two antigen-specific targeting regions that bind at least two different antigens, each of said regions individually comprising an scFv, (ii) an extracellular spacer domain, (iii) a transmembrane domain, (iv) a co-stimulatory domain, and (v) an intracellular signaling domain;
- and
- b. a nucleic acid encoding a therapeutic control.
A genetically engineered cell comprising
- a. a bispecific chimeric antigen receptor-encoding polynucleotide comprising a nucleic acid encoding (i) at least two antigen-specific targeting regions that bind at least two different antigens, each of said regions individually comprising an scFv, (ii) an extracellular spacer domain, (iii) a transmembrane domain, (iv) a co-stimulatory domain, and (v) an intracellular signaling domain;
- and
- b. a polynucleotide encoding a therapeutic control.
Dependencies are inferred from the claim text.