PEPTIDIC CHIMERIC ANTIGEN RECEPTOR T CELL SWITCHES AND USES THEREOF
Disclosed herein are chimeric antigen receptor effector cells (CAR-ECs) and CAR-EC switches. The switchable CAR-ECs are generally T cells. The one or more chimeric antigen receptors may recognize a peptidic antigen on the CAR-EC switch. The CAR-ECs and switches may be used for the treatment of a condition in a subject in need thereof.
1 . A chimeric antigen receptor-effector cell switch comprising:
a. a peptidic antigen that binds a chimeric antigen receptor on an effector cell; and
b. a targeting moiety that binds a cell surface molecule on a target cell.
2 . The chimeric antigen receptor-effector cell switch of claim 1 , wherein the peptidic antigen is based on or derived from a naturally occurring peptide.
3 . The chimeric antigen receptor-effector cell switch of claim 2 , wherein the peptidic antigen is based on or derived from a non-human peptide.
4 . The chimeric antigen receptor-effector cell switch of claim 2 , wherein the peptidic antigen is based on or derived from a eukaryotic peptide.
5 . The chimeric antigen receptor-effector cell switch of claim 2 , wherein the peptidic antigen is based on or derived from a peptide, wherein the peptide is expressed by a yeast.
6 . The chimeric antigen receptor-effector cell switch of claim 2 , wherein the peptidic antigen is based on or derived from a yeast transcription factor GCN4.
7 . The chimeric antigen receptor-effector cell switch of claim 1 , wherein the peptidic antigen comprises a non-naturally occurring peptide.
8 . The chimeric antigen receptor-effector cell switch of claim 7 , wherein the peptidic antigen comprises a synthetic peptide tag.
9 . The chimeric antigen receptor-effector cell switch of claim 1 , wherein the peptidic antigen is based on or derived from a sequence selected from SEQ ID NOs: 2-7.
10 . The chimeric antigen receptor-effector cell switch of claim 1 , wherein the peptidic antigen comprises a sequence that is at least about 50% homologous to a peptide sequence selected from SEQ ID NOs: 2-7.
11 . The chimeric antigen receptor-effector cell switch of claim 1 , wherein the targeting moiety comprises a targeting peptide.
12 . The chimeric antigen receptor-effector cell switch of claim 1 , wherein the targeting moiety comprises a targeting antibody or antibody fragment.
13 . The chimeric antigen receptor-effector cell switch of claim 12 , wherein the targeting antibody or antibody fragment is selected from the group consisting of: an immunoglobulin, an Fc null immunoglobulin, and a Fab, and fragments thereof.
14 . The chimeric antigen receptor-effector cell switch of claim 12 , wherein the targeting moiety is selected from the group consisting of: an anti-EGFR antibody, an anti-Her2 antibody, anti-EGFRvIII antibody, an anti-CD33 antibody, an anti-CLL-1 antibody, an anti-CEA antibody, an anti-CD19 antibody, an anti-CD22 antibody, an anti-BCMA antibody, and an anti-CS1 antibody, and fragments thereof.
15 . The chimeric antigen receptor-effector cell switch of claim 12 , wherein the targeting antibody or antibody fragment comprises a light chain and a heavy chain pair, wherein the light chain and heavy chain are encoded by nucleic acid sequences based on or derived from nucleic acid sequence pairs selected from the group consisting of: SEQ ID NOs: 8 and 9; SEQ ID NOs: 8 and 10; SEQ ID NOs: 11 and 12; SEQ ID NOs. 13 and 14; SEQ ID NOs: 15 and 16; SEQ ID NOs: 17 and 18; and SEQ ID NOs: 19 and 20.
16 . The chimeric antigen receptor-effector cell switch of claim 12 , wherein the targeting antibody or antibody fragment comprises a light chain and a heavy chain pair, wherein the light chain and heavy chain are encoded by amino acid sequences based on or derived from amino acid sequence pairs selected from the group consisting of: SEQ ID NOs: 21 and 22; SEQ ID NOs: 23 and 24; SEQ ID NOs. 25 and 26; SEQ ID NOs: 27 and 28; and SEQ ID NOs: 27 and 29.
17 . The chimeric antigen receptor-effector cell switch of claim 12 , wherein the chimeric antigen receptor-effector cell switch comprises a light chain and a heavy chain pair, wherein the light chain and heavy chain are encoded by amino acid sequences based on or derived from amino acid sequence pairs selected from the group consisting of: SEQ ID NOs: 30 and 29; SEQ ID NOs: 36 and 29; SEQ ID NOs: 31 and 28; SEQ ID NOs: 27 and 32; SEQ ID NOs: 27 and 33; SEQ ID NOs: 27 and 34; and SEQ ID NOs: 27 and 35.
18 . The chimeric antigen receptor-effector cell switch of claim 12 , wherein the peptidic antigen is fused to a terminus of the targeting antibody or antibody fragment.
19 . The chimeric antigen receptor-effector cell switch of claim 12 , wherein the peptidic antigen is fused to a region of the targeting antibody or antibody fragment selected from the group consisting of: an N terminus of a light chain, a C terminus of a light chain, an N terminus of a heavy chain, a C terminus of a Fab heavy chain, and a C terminus of a constant region heavy chain.
20 . The chimeric antigen receptor-effector cell switch of claim 1 , wherein the peptidic antigen is grafted into the targeting moiety.