Chimeric antigen receptors and modified cells comprising the same
AssigneeSingapore Health Services Pte Ltd
InventorSalvatore ALBANI
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Abstract
The present invention relates to a chimeric antigen receptor (CAR) comprising an extracellular domain that binds to one or more inflammation associated factor(s), a transmembrane/hinge domain and an intracellular domain. In a specific embodiment, a T regulatory (Treg) cell expressing a construct encoding said CAR which further comprising a Fox3p and a CAR activation-dependent NF-AT promoter that drives the expression of interleukin-10 and TGF-beta. It also relate to the methods of producing the CAR, the Treg cells expressing said CAR and the use of said CAR to treat autoimmune diseases such as transplant rejection, a graft versus host disease (GVHD) and cytokine release syndrome..
Claims103
A chimeric antigen receptor (CAR) comprising an extracellular domain, a transmembrane domain, and an intracellular domain, wherein the extracellular domain binds one or more inflammation associated factor(s).
The chimeric antigen receptor of any one of the preceding claims, wherein the chimeric antigen receptor further comprises a hinge region located between the extracellular domain and the transmembrane domain.
The chimeric antigen receptor of any one of the preceding claims, wherein the transmembrane domain is a transmembrane domain of a protein selected from the group consisting of CD28, CD28T, OX-40, 4-1BB/CD137, CD2, CD7, CD27, CD30, CD40, programmed death-1 (PD-1), inducible T cell co-stimulator (ICOS), lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18), CD3 gamma, CD3 delta, CD3 epsilon, CD247, CD276 (B7-H3), LIGHT, (TNFSF14), NKG2C, Ig alpha (CD79a), DAP-10, Fc gamma receptor, MHC class 1 molecule, TNF receptor proteins, an Immunoglobulin protein, cytokine receptor, integrins, and functional variations/fragments thereof.
The chimeric antigen receptor of any one of the preceding claims, wherein the extracellular domain and/or the intracellular domain comprise a self-cleaving peptide.
The chimeric antigen receptor of any one of the preceding claims, wherein the hinge region comprises an IgG4 hinge, the transmembrane domain comprises a CD28 transmembrane domain, the co-stimulatory domain is the intracellular signalling domain of CD28, the signalling domain comprises the intracellular signalling domain of CD3 zeta, the intracellular domain comprises FOXP3, wherein the intracellular signalling domain of CD3 zeta and the FOX3P are separated by the self-cleaving peptide TA2.
The chimeric antigen receptor of any one of the preceding claims, wherein the hinge region comprises an IgG4 hinge, the transmembrane domain comprises a CD28 transmembrane domain, the co-stimulatory domain is the intracellular signalling domain of CD28, the signalling domain comprises the intracellular signalling domain of CD3 zeta.
The chimeric antigen receptor of any one of the preceding claims, wherein the chimeric antigen receptor comprises the sequence of SEQ ID NO:
- 12.
A first polynucleotide encoding the chimeric antigen receptor of any one of the preceding claims.
A vector comprising the sequence as set forth in SEQ ID NO:
- 14 or 15.
Dependencies are inferred from the claim text.