Chimeric receptors and methods of use thereof
AssigneesAmgen Inc., Kite Pharma, Inc.
InventorsJed WILTZIUS, Ruben ALVAREZ RODRIGUEZ
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Abstract
Antigen binding molecules, chimeric receptors, and engineered immune cells are disclosed in accordance with the invention. The invention further relates to vectors, compositions, and methods of treatment and/or detection using the antigen binding molecules and engineered immune cells.
Claims80
A chimeric antigen receptor comprising an antigen binding molecule that specifically binds to CLL-1, wherein the antigen binding molecule comprises at least one of:
- a) a variable heavy chain CDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 17, 51, 73, and 95,
- b) a variable heavy chain CDR2 comprising an amino acid sequence selected from the group consisting of SEQ NOs 18, 52, 74, and 96,
- c) a variable heavy chain CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs 19, 53, 75, and 97,
- d) a variable light chain CDR1 comprising an amino acid sequence selected from the group consisting of SEQ NOs:
- 22, 56, 78, and 100,
- e) a variable light chain CDR2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs. 23, 57, 79, and 101,
- f) a variable light chain CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID Nos. 24, 58, 80, and 102.
A chimeric antigen receptor comprising at least one of:
- (a) a VH region comprising the amino acid sequence of SEQ ID NO:
- 16 and a VL region comprising the amino acid sequence of SEQ ID NO:
- 21;
- (b) a VH region comprising the amino acid sequence of SEQ ID NO:
- 50 and a VL region comprising the amino acid sequence of SEQ ID NO:
- 55;
- (c) a VH region comprising the amino acid sequence of SEQ ID NO:
- 72 and a VL region comprising the amino acid sequence of SEQ ID NO:
- 77;
- (d) a VH region comprising the amino acid sequence of SEQ ID NO:
- 94 and a VL region comprising the amino acid sequence of SEQ ID NO:
- 99;
- wherein the VH and VL region is linked by at least one linker.
An isolated polynucleotide comprising at least one of:
- SEQ ID NO. 27;
- SEQ ID NO. 31;
- SEQ ID NO. 35;
- SEQ ID NO, 39;
- SEQ ID NO. 43;
- SEQ ID NO. 47;
- SEQ ID NO. 61;
- SEQ ID NO. 65;
- SEQ ID NO. 69;
- SEQ ID NO. 83;
- SEQ ID NO. 87;
- SEQ ID NO. 91;
- SEQ ID NO. 105;
- SEQ ID NO. 109;
- SEQ ID NO. 113;
- SEQ ID NO, 117;
- SEQ ID NO. 121;
- and SEQ ID NO. 125.
An isolated polypeptide comprising the amino acid sequence set forth in at least one of:
- SEQ ID NO. 28;
- SEQ ID NO. 32;
- SEQ ID NO. 36;
- SEQ ID NO. 40;
- SEQ ID NO. 44;
- SEQ ID NO. 48;
- SEQ ID NO, 62;
- SEQ ID NO. 66;
- SEQ ID NO. 70;
- SEQ ID NO, 84;
- SEQ ID NO. 88;
- SEQ ID NO. 92;
- SEQ ID NO. 106;
- SEQ ID NO. 110;
- SEQ ID NO. 114;
- SEQ ID NO. 118;
- SEQ ID NO. 122;
- and SEQ ID NO. 126.
An isolated polynucleotide encoding a chimeric antigen receptor (CAR) or T cell receptor (TCR) comprising an antigen binding molecule that specifically binds to CLL-1, wherein the antigen binding molecule comprises a variable heavy chain CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 19, 53, 75, and 97.
An isolated polynucleotide encoding a chimeric antigen receptor (CAR) or T cell receptor (TCR), said CAR or TCR comprising an antigen binding molecule that specifically binds to CLL-1, wherein the antigen binding molecule comprises a variable light chain CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 24, 58, 80, and 102.
An isolated polynucleotide encoding a chimeric antigen receptor (CAR) or T cell receptor (TCR) comprising an antigen binding molecule that specifically binds to CLL-1, wherein the antigen binding molecule heavy chain comprises CDR1 (SEQ ID NO. 17), CDR2 (SEQ ID NO. 18), and CDR3 (SEQ ID NO. 19) and the antigen binding molecule light chain comprises CDR1 (SEQ ID NO. 22), CDR2 (SEQ ID NO. 23), and CDR3 (SEQ ID NO. 24).
An isolated polynucleotide encoding a chimeric antigen receptor (CAR) or T cell receptor (TCR) comprising an antigen binding molecule that specifically binds to CLL-1, wherein the antigen binding molecule heavy chain comprises CDR1 (SEQ ID NO. 51), CDR2 (SEQ ID NO. 52), and CDR3 (SEQ ID NO. 53) and the antigen binding molecule light chain comprises CDR1 (SEQ ID NO. 56), CDR2 (SEQ ID NO. 57), and CDR3 (SEQ ID NO. 58).
An isolated polynucleotide encoding a chimeric antigen receptor (CAR) or T cell receptor TCR) comprising an antigen binding molecule that specifically binds to CLL-1, wherein the antigen binding molecule heavy chain comprises CDR1 (SEQ ID NO. 73), CDR2 (SEQ ID NO. 74), and CDR3 (SEQ ID NO. 75) and the antigen binding molecule light chain comprises CDR1 (SEQ ID NO. 78), CDR2 (SEQ ID NO. 79), and CDR3 (SEQ ID NO. 80).
An isolated polynucleotide encoding a chimeric antigen receptor (CAR) or T cell receptor (TCR) comprising an antigen binding molecule that specifically binds to CLL-1, wherein the antigen binding molecule heavy chain comprises CDR1 (SEQ ID NO. 95), CDR2 (SEQ ID NO. 96), and CDR3 (SEQ ID NO. 97) and the antigen binding molecule light chain comprises CDR1 (SEQ ID NO. 100), CDR2 (SEQ ID NO. 101), and CDR3 (SEQ ID NO. 102).
An isolated polynucleotide encoding a chimeric antigen receptor (CAR) or T cell receptor (TCR) comprising an antigen binding molecule that specifically binds to CLL-1, wherein the antigen binding molecule comprises:
- (a) a heavy chain variable region (VH) complementarity determining region (CDR) 1 comprising the amino acid sequence GX2X3X4X5X6X7X8X9(SEQ ID NO:
- 134), wherein:
- X2 is G, F, or Y;
- X3 is S or T;
- X4 is I, F, or L,
- X5 is S or T;
- X6 is not present or S;
- X7 is not present or G;
- X8 is not present or E or G;
- and
- X9 is F, L, or Y;
- (b) a heavy chain variable region (VH) complementarity determining region (CDR) 2 comprising the amino acid sequence X1X2X3X4X5X6 (SEQ ID NO:
- 135), wherein:
- X1 is D, H, S, or Y;
- X2 is H, P, or Y;
- X3 is D, E, or S;
- X4 is D or G;
- X5 is G or S;
- and
- X6 is not present of D or E;
- (c) a heavy chain variable region (VH) complementarity determining region (CDR) 3, comprising the amino acid sequence X1X2X3X4X5X6X7X8X9X10X11X12DY (SEQ ID NO:
- 136), wherein:
- X1 is E or L.;
- X2 is R, S, or V;
- X3 is R or Y;
- X4 is C, G, or S;
- X5 is not present or G or I;
- X6 is not present or G;
- X7 is not present or D;
- X8 is not present or C;
- X9 is not present or W or Y;
- X10 is not present or P or S;
- X11 is not present or G or Y;
- and
- X12 is F or R;
- (d) a light chain variable region (VL) CDR1 comprising the amino acid sequence X1ASQX5X6X7X8X9LX11 (SEQ ID NO:
- 137), wherein
- X1 is Q or R;
- X5 is D or S;
- X6 is I or V;
- X7 is N or S;
- X8 is N or S;
- X9 is F, L, or Y;
- and
- X11 is N or T;
- (e) a light chain variable region (VL) CDR2 comprising the amino acid sequence X1ASX4X5X6X7(SEQ ID NO:
- 138), wherein
- X1 is D or G;
- X4 is N, S, or T;
- X5 is L or R;
- X6 is A, E, or K;
- and
- X7 is S or T;
- and/or
- (f) a light chain variable region (VL) CDR3 comprising the amino acid sequence QQX3X4X5X6PX8T (SEQ ID NO:
- 139), wherein
- X3 is S or Y;
- X4 is D, G, or Y;
- X5 is N, S, or T;
- X7 is L, T, or Y;
- and
- X8 is F or I.
A method of treating a disease or disorder in a subject in need thereof comprising administering to the subject the polypeptide according to 40.
Dependencies are inferred from the claim text.