CD19 AND CD22 CHIMERIC ANTIGEN RECEPTORS AND USES THEREOF
The present disclosure provides compositions and methods for treating diseases associated with expression of CD19 and/or CD22, e.g., by administering a recombinant T cell or natural killer (NK) cell comprising a CD22 CAR and a CD19 CAR as described herein. The disclosure also relates to CAR molecules specific to CD22 and/or CD19, methods of making a cell comprising the same and vectors encoding the same.
1 . A chimeric antigen receptor (CAR) molecule, which comprises:
(a) a first CAR comprising a first antigen binding domain which binds to CD22 and a first transmembrane domain; a first costimulatory signaling domain; and/or a first primary signaling domain; and
(b) a second CAR comprising a second antigen binding domain which binds to CD19 and a second transmembrane domain; a second costimulatory domain; and/or a second primary signaling domain,
wherein the CAR molecule comprising the first CAR and the second CAR comprises the amino acid sequence of SEQ ID NO: 12 or 16, or an amino acid sequence having at least 95%, 96%, 97%, 98%, or 99% identity thereto.
2 . The CAR molecule of claim 1 , wherein the first CAR comprises:
(a) a first antigen binding domain which binds to CD22; a first transmembrane domain; and a first costimulatory signaling domain;
(b) a first antigen binding domain which binds to CD22; a first transmembrane domain; and a first primary signaling domain; or
(c) a first antigen binding domain which binds to CD22; a first transmembrane domain; a first costimulatory signaling domain, and a first primary signaling domain.
3 . The CAR molecule of claim 1 , wherein the second CAR comprises:
(a) a second antigen binding domain which binds to CD19; a second transmembrane domain; and a second costimulatory signaling domain;
(b) a second antigen binding domain which binds to CD19; a second transmembrane domain; and a second primary signaling domain; or
(c) a second antigen binding domain which binds to CD19; a second transmembrane domain; a second costimulatory signaling domain; and a second primary signaling domain.
4 .- 12 . (canceled)
13 . The CAR molecule of claim 1 , which comprises the amino acid sequence of SEQ ID NO: 12.
14 .- 23 . (canceled)
24 . A pharmaceutical composition comprising the CAR molecule of claim 1 wherein the pharmaceutical composition comprises an excipient, a carrier, a diluent and/or a stabilizer.
25 . A method of providing anti-tumor immunity, comprising administering to a subject in need thereof, an effective amount of a cell comprising the CAR molecule of claim 1 .
26 . A method of treating a subject having a disease associated with an antigen, comprising administering to the subject in need thereof, an effective amount of a cell comprising the CAR molecule of claim 1 , wherein the disease is a hematological cancer.
27 . The method of claim 25 , wherein the cell is a T cell.
28 .- 29 . (canceled)
30 . The method of claim 26 , wherein the hematological cancer is selected from the group consisting of acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (BALL), small lymphocytic lymphoma (SLL), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), B cell prolymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B cell lymphoma (DLBCL), follicular lymphoma, hairy cell leukemia, small cell-lymphoma, large cell-follicular lymphoma, a malignant lymphoproliferative condition, MALT lymphoma, Marginal zone lymphoma, multiple myeloma, myelodysplasia, or myelodysplastic syndrome, myeloproliferative neoplasm, non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenstrom macroglobulinemia, preleukemia, and a combination thereof.
31 . The method of claim 26 , wherein the hematological cancer is pediatric BALL.
32 . The method of claim 26 , wherein the hematological cancer is adult BALL.
33 .- 34 . (canceled)
35 . The method of claim 25 , wherein the cell is an NK cell.
36 . The method of claim 26 , wherein the cell is a T cell.
37 . The method of claim 26 , wherein the cell is an NK cell.
38 . The CAR molecule of claim 1 , which comprises the amino acid sequence of SEQ ID NO: 16.