CD5 chimeric antigen receptor for adoptive T cell therapy
Embodiments of the disclosure include methods and compositions related to immunotherapy that targets CD5. In particular embodiments, immune cells engineered to comprise a chimeric antigen receptor (CAR) that targets CD5 are contemplated, and uses thereof. In particular embodiments, the immune cells expressing the CAR do not commit fratricide to any great extent against T cells that express CD5 and which are endogenous to an individual receiving the immune cells.
1. As a composition of matter, immune cells that express a chimeric antigen receptor (CAR) that targets CD5, wherein the CAR comprises the amino acid sequence of SEQ ID NO:13 or SEQ ID NO:14.
2. The composition of claim 1 , wherein the cells are T cells, NK cells, dendritic cells, or a mixture thereof.
3. The composition of claim 1 , wherein the CAR is expressed from a recombinant polynucleotide.
4. The composition of claim 3 , wherein the polynucleotide further comprises a suicide gene, a cytokine, an additional CAR, a cytokine receptor, or a chimeric cytokine receptor.
5. The composition of claim 1 , wherein the immune cells comprise a polynucleotide that comprises a suicide gene, a cytokine, an additional CAR, a cytokine receptor, or a chimeric cytokine receptor, wherein said polynucleotide is a different molecule than the polynucleotide that expresses the CAR that targets CD5.
6. The composition of claim 1 , wherein the CAR comprises a co-stimulatory molecule endodomain selected from the group consisting of CD28, CD27, 4-1BB, OX40, ICOS, and a combination thereof.
7. The composition of claim 1 , wherein the CAR comprises a co-stimulatory molecule endodomain that is not 4-1BB.
8. The composition of claim 4 , wherein the additional CAR is an activating CAR or an inhibitory CAR.
9. The composition of claim 2 , wherein said T cells are CD4+ T cells.
10. The composition of claim 2 , wherein said T cells are CD8+ T cells.
11. The composition of claim 2 , wherein said T cells are Treg cells.
12. The composition of claim 1 , wherein the CAR comprises one or more scFvs, in addition to an scFV comprised in SEQ ID NO:13 or SEQ ID NO:14.
13. The composition of claim 12 , wherein the one or more scFvs in addition to the scFv comprised in SEQ ID NO:13 or SEQ ID NO:14 targets CD19, CD20, CD22, Kappa or light chain, Glypican-3, CD30, CD33, CD123, CD38, ROR1, ErbB2, ErbB3/4, EGFR VIII, carcinoembryonic antigen, EGP2, EGP40, mesothelin, TAG72, PSMA, NKG2D ligands, B7-H6, IL-13 receptor α2, IL-11 receptor R α, MUC1, MUC16, CA9, GD2, GD3, HMW-MAA, CD171, Lewis Y, G250/CAIX, HLA-AI MAGE A1, HLA-A2 NY-ESO-1, PSC1, folate receptor-α, CD44v7/8, 8H9, NCAM, VEGF receptors, 5T4, Fetal AchR, NKG2D ligands, CD44v6 or CD7.
14. The composition of claim 1 , wherein the CAR comprises a transmembrane domain selected from the group consisting of CD3-zeta, CD28, CD8α, CD4, or a combination thereof.
15. The composition of claim 1 , wherein the CAR comprises a spacer derived from IgG CH3 without the CH2 domain.
16. The composition of claim 1 , wherein the spacer is derived from CD8α.
17. The composition of claim 1 , wherein the CAR comprises amino acid sequence of SEQ ID NO:14.
18. The composition of claim 1 , wherein the CAR comprises the amino acid sequence of SEQ ID NO:13.
19. The composition of claim 1 , wherein the CAR comprises a CD5scFv, a leader sequence, a CH2+CH3 IgG1 spacer, a hinge, CD28 transmembrane domain, CD28 co-stimulatory endodomain, and CD3zeta.