CD8 binding agents
The present invention relates, in part, to agents that bind CD8 and their use as therapeutic and diagnostic agents. The present invention further relates to pharmaceutical compositions comprising the CD8 binding agents and their use in the treatment of various diseases, including, for example, cancers.
1. A CD8 binding agent comprising at least one targeting moiety comprising three complementarity determining regions (CDR1, CDR2, and CDR3), wherein:
(a) CDR1 comprises an amino acid sequence selected from GFTFDDYAMS (SEQ ID NO:12) and GFTFDDYAIG (SEQ ID NO:13);
(b) CDR2 comprises an amino acid sequence selected from TINWNGGSAEYAEPVKG (SEQ ID NO:14) and CIRVSDGSTYYADPVKG (SEQ ID NO:15); and
(c) CDR3 comprises an amino acid sequence selected from KDADLVWYNLS (SEQ ID NO:16), KDADLVWYNLR (SEQ ID NO:17), and AGSLYTCVQSIVVVPARPYYDMDY (SEQ ID NO:18),
wherein the targeting moiety is a single-domain antibody.
2. The CD8binding agent of claim 1 , wherein the single-domain antibody is a VHH, or a humanized VHH.
3. The CD8 binding agent of claim 1 , wherein the targeting moiety comprises a CDR1 comprising the amino acid sequence of GFTFDDYAMS (SEQ ID NO:12), a CDR2 comprising the amino acid sequence of TINWNGGSAEYAEPVKG (SEQ ID NO:14), and a CDR3 comprising the amino acid sequence of KDADLVWYNLS (SEQ ID NO:16).
4. The CD8 binding agent of claim 3 , comprising an amino acid sequence having at least 95% sequence similarity with SEQ ID NO:19.
5. The CD8 binding agent of claim 1 , wherein the targeting moiety comprises a CDR1 comprising the amino acid sequence of GFTFDDYAMS (SEQ ID NO:12), a CDR2 comprising the amino acid sequence of TINWNGGSAEYAEPVKG (SEQ ID NO:14), and a CDR3 comprising the amino acid sequence of KDADLVWYNLR (SEQ ID NO:17).
6. The CD8 binding agent of claim 5 , comprising an amino acid sequence having at least 95% sequence similarity with SEQ ID NO:20.
7. The CD8 binding agent of claim 1 , wherein the targeting moiety comprises a CDR1 comprising the amino acid sequence of GFTFDDYAIG (SEQ ID NO:13), a CDR2 comprising the amino acid sequence of CIRVSDGSTYYADPVKG (SEQ ID NO:15), and a CDR3 comprising the amino acid sequence of AGSLYTCVQSIVVVPARPYYDMDY (SEQ ID NO:18).
8. The CD8 binding agent of claim 7 , comprising an amino acid sequence having at least 95% sequence similarity with SEQ ID NO:21.
9. The CD8 binding agent of claim 1 , wherein the CD8 binding agent further comprises one or more additional targeting moieties.