CAR-CD123 vector and uses thereof
The present invention relates to a chimeric antigen receptor (CAR) comprising: an extracellular domain and transmembrane domain of human CD19, an antigen binding domain, a spacer domain, a transmembrane domain, and a cytoplasmic domain, preferably wherein the CAR is a CD123 specific CAR (CD123 CAR) and the antigen binding domain comprises VL and/or VH from a monoclonal anti-CD123 antibody.
The present invention relates to a vector comprising the nucleotide sequence which encodes the sequence ΔCD19-2A-CAR-CD123-ΔCD34.CD8.41BB.CD3ζ, wherein said vector is a DNA vector, an RNA vector, a plasmid, a lentiviral vector, an adenoviral vector, a retroviral or a non-viral vector. The present invention relates to a cell, such as a T cell, such as an alpha / beta and gamma / delta T cell, NK cells, NK-T cells, comprising the aforementioned vector or plasmid. Inventors have designed a bicistronic vector, allowing the simultaneous expression of three transgenes, namely ΔCD19, ΔCD34 and CARCD123. The ΔCD19 gene can be used as a transduction marker and inducible suicide gene because it can target FDA / EMA approved anti-CD19 antibodies. The use of the invention in the treatment of CD123 + tumors such as acute myeloid leukemia, myelodysplastic syndrome, ALL-B, etc.
- CAR cells (T alpha / beta and gamma / delta, NK cells, NK-T cells), including the vector or plasmid related to this invention, can be used effectively in the treatment of CD123+ tumors such as AML, B-lymphoid leukaemia, BPDCN, myelodysplastic syndrome,hairy cell leukaemia, ecc;
- Personalized therapy.
- Higher and more stable expression of CAR-CD123 of transduced cells expanded in IL7 / IL15;
- The ΔCD19 gene can be used as a transduction marker and inducible suicide gene;
- The CD34 and CD19 epitopes simply trace CAR-CD123 T and / or CAR-CD123 NK cells;
- It has potent lytic activity on CD123 + tumors.