Single domain antibodies targeting CD1d
The invention relates to compounds, in particular polypeptides that specifically bind to the non-classical MHC protein CD1d and modulate CD1d-mediated biological functions. The invention in particular relates to such compounds and polypeptides comprising or consisting of at least one single domain antibody, and wherein at least one single domain antibody specifically binds to CD1d. Also provided is for methods and use employing such compounds, polypeptides and/or single-domain antibodies.
1. A compound comprising at least one single-domain antibody which binds to human CD1d, wherein the single-domain antibody comprises complementarity determining regions CDR1, CDR2 and CDR3, wherein CDR1 comprises the amino acid sequence set forth in SEQ ID NO:33, CDR2 comprises the amino acid sequence set forth in SEQ ID NO:54 and CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 75.
2. A compound according to claim 1 , wherein the compound comprises the amino acid sequence set forth in SEQ ID NO:12, or a conservative sequence variant thereof.
3. A compound according to claim 1 , wherein the compound comprises a label, wherein an pharmaceutical active agent is linked to the compound, wherein the compound is a bivalent or multivalent compound, wherein the compound is fused to an antigen, a peptide or a nucleotide sequence, wherein the compound is a liposome, wherein the compound is a virus, and/or wherein the compound is a nanoparticle.
4. A compound according to claim 1 , wherein the compound binds to human CD1d but not to human CD1a, human CD1b and/or human CD1c.
5. A compound according to claim 1 , wherein
the compound is capable of inducing activation of CD1d-restricted T cells, including invariant natural killer T-cells, and/or stimulating alpha-galactosyl ceramide, induced activation of CD1d-restricted T cells, including invariant natural killer T-cells.
6. A compound according to claim 1 , wherein the compound is a single domain antibody.
7. A compound according to claim 1 , wherein the single domain antibody is a humanized single domain antibody.
8. A compound according to claim 1 , for use in medical treatment, or for in vivo use as a diagnostic agent.
9. A pharmaceutical composition comprising a compound according to claim 1 .
10. A nucleotide sequence that encodes a compound according to claim 1 .
11. An isolated host cell or non-human organism comprising a nucleotide sequence encoding a compound according to claim 1 .
12. The host cell according to claim 11 that produces said compound or part thereof.
13. A method for preparing a compound comprising at least one single-domain antibody which binds to human CD1d, wherein the method comprises culturing the host cell of claim 12 to express the compound or part thereof; and obtaining the compound.
14. An antibody that comprises a CDR1, CDR2 and CDR3, wherein the CDR1 has the amino acid sequence set forth in SEQ ID NO:33, the CDR2 has the amino acid sequence set forth in SEQ ID NO:54 and CDR3 has the amino acid sequence set forth in SEQ ID NO:75.
15. A compound according to claim 1 , wherein the compound comprises the amino acid sequence set forth in SEQ ID NO: 12.
16. A compound according to claim 1 , wherein the compound further comprises an additional single domain antibody.
17. A compound according claim 1 , wherein the compound is a bispecific or multispecific compound.
18. A compound according claim 1 , wherein the compound is linked to another antibody.