Bispecific chimeric antigen receptors and methods of use thereof to treat cancer
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.
Claims87
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 a single-domain antibody.
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 a single-domain antibody, and
- wherein each antigen-specific targeting region binds a different antigen.
The bispecific chimeric antigen receptor of claim44, wherein the cleavable linker is a 2A linker or a 2A-like linker.
A bispecific chimeric antigen receptor comprising the sequence set forth in SEQ ID NO:
- 2, 8 or 11.
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 a single-domain antibody.
The bispecific chimeric antigen receptor of claim73, wherein the CCR comprises any one or more of (i) IL-7 cytokine-linker- IL7Rα, (ii) IL-7 cytokine-linker-extracellular domain of IL-7Rα-transmembrane domain of IL-7Rαcytoplasmic domain of IL-2Rβ, (iii) IL-7cytokine-linker-IL2Rβ, and (iv) combinations thereof.
The bispecific chimeric antigen receptor of claim77, wherein the antigen specific for diabetes comprises L-1β, CD3, or a combination thereof.
Dependencies are inferred from the claim text.