Bi-specific aptamer
Provided are aptamers and aptamer compositions and particularly, although not exclusively, to a bi-specific aptamer capable of binding a tumor cell antigen and an immune cell surface protein.
1. A bi-specific aptamer capable of binding a tumor cell antigen and an immune cell surface protein, wherein the bi-specific aptamer comprises a first aptamer complexed with a second aptamer, and further wherein
the immune cell surface protein is CD8.
2. The bi-specific aptamer of claim 1 , wherein the tumor cell antigen is TfR.
3. The bi-specific aptamer of claim 1 , wherein the bi-specific aptamer comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 30.
4. The bi-specific aptamer of claim 1 , wherein the bi-specific aptamer comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 28.
5. The bi-specific aptamer of claim 1 , wherein one or more bases or nucleotides are chemically modified.
6. The bi-specific aptamer of claim 1 , wherein one or more nucleotides are chemically modified at the 2′ position of ribose.
7. A complex of a bi-specific aptamer according to claim 1 and a tumor cell expressing a tumor cell antigen to which the bi-specific aptamer is capable of binding.
8. A complex of a bi-specific aptamer according to claim 1 and an immune cell expressing an immune cell surface protein to which the bi-specific aptamer is capable of binding, wherein the immune cell surface protein is CD8.
9. A complex of a bi-specific aptamer according to claim 1 , a tumor cell expressing a tumor cell antigen to which the bi-specific aptamer is capable of binding, and an immune cell expressing an immune cell surface protein to which the bi-specific aptamer is capable of binding, wherein the immune cell surface protein is CD8.
10. A complex of a bi-specific aptamer and an immune cell expressing an immune cell surface protein to which the bi-specific aptamer is capable of binding, wherein:
(a) the immune cell is a T-cell;
(b) the bi-specific aptamer is capable of binding a tumor cell antigen and the immune cell surface protein;
(c) the bi-specific aptamer comprises a first aptamer complexed with a second aptamer; and
(d) the tumor cell antigen is TfR or the immune cell surface protein is CD8.
11. A pharmaceutical composition comprising a bi-specific aptamer according to claim 1 and a pharmaceutically acceptable carrier, diluent or excipient.
12. A bi-specific aptamer according to claim 1 for use in a method of medical treatment.
13. A bi-specific aptamer according to claim 1 for use in a method of treatment of cancer.
14. A bi-specific aptamer for use in a method of treatment of cancer, wherein:
(a) the cancer is a pancreatic cancer;
(b) the bi-specific aptamer is capable of binding a tumor cell antigen and the immune cell surface protein;
(c) the bi-specific aptamer comprises a first aptamer complexed with a second aptamer; and
(d) the tumor cell antigen is TfR or the immune cell surface protein is CD8.
15. The bi-specific aptamer for use in a method of treatment of cancer according to claim 13 , wherein the cancer overexpresses at least one of HSP70, vimentin, HSP90, Tfr or PDGFR-a.
16. The bi-specific aptamer of claim 1 , wherein the bi-specific aptamer comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 29.
17. The bi-specific aptamer of claim 1 , wherein the tumor cell antigen is HSP70.
18. The bi-specific aptamer of claim 1 , wherein the tumor cell antigen is vimentin.
19. The bi-specific aptamer of claim 1 , wherein the tumor cell antigen is HSP90.
20. The bi-specific aptamer of claim 1 , wherein the tumor cell antigen is PDGFR.
21. The bi-specific aptamer of claim 1 , wherein the bi-specific aptamer comprises the nucleic acid sequence of SEQ ID NO: 8.