Humanized anti-CD19 antibody and use thereof with chimeric antigen receptor
Embodiments herein relate to humanized CD19 antibodies and disease treatment using the antibodies. For example, a subject having a CD19 positive tumor may be administered a therapeutically effective amount of the humanized antibody.
1. An isolated nucleic acid sequence encoding a humanized antibody or antigen binding fragment thereof, wherein the humanized antibody or antigen binding fragment thereof comprising a heavy chain variable (HCV) sequence having the amino acid sequence of SEQ ID NO: 27, and a light chain variable (LCV) sequence having the amino acid sequence of SEQ ID NO: 34, and wherein the humanized antibody or antigen binding fragment thereof binds CD19.
2. The isolated nucleic acid sequence of claim 1 , wherein the antigen binding fragment is selected from the group consisting of a Fab, Fab′, Fab′-SH, Fv, scFv, F(ab)2 and a diabody.
3. A vector comprising the isolated nucleic acid sequence of claim 1 .
4. An isolated cell comprising the vector of claim 3 .
5. The vector of claim 3 , wherein the vector is an expression vector comprising control sequences operably linked to the isolated nucleic acid.
6. An isolated cell comprising the expression vector of claim 5 .
7. A composition comprising a population of the cells of claim 4 .
8. The composition of claim 7 , wherein the cells comprise T cells.
9. The composition of claim 7 , wherein the composition is a pharmaceutical composition.
10. A composition comprising a population of the cells of claim 6 .
11. The composition of claim 10 , wherein the cells comprise T cells.
12. The composition of claim 11 , wherein the composition is a pharmaceutical composition.
13. A chimeric antigen receptor (CAR) comprising a scFv comprising a HCV sequence having the amino acid sequence of SEQ ID NO: 27 and a LCV sequence having the amino acid sequence of SEQ ID NO: 34, and wherein the CAR binds CD19.
14. The CAR of claim 13 , wherein the CAR comprises an antigen binding domain comprising the scFv, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain.
15. The CAR of claim 14 , wherein the CD3 zeta signaling domain comprises the amino acid sequence of SEQ ID NO: 42 or 45.
16. The CAR of claim 14 , wherein the costimulatory signaling region comprises the intracellular domain of a costimulatory molecule selected from the group consisting of CD27, CD28, 4-IBB, OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, a ligand that specifically binds with CD83, and any combination thereof.