Antibody fusion protein and related compositions for targeting cancer
Disclosed herein are compositions comprising a polypeptide with at least two domains, wherein the first domain is capable of binding CD3 and the second domain is capable of binding to a cancer cell. Also disclosed herein are methods of treating cancer in a subject, comprising: providing a composition comprising a polypeptide with at least two domains, wherein the first domain is capable of binding CD3 and the second domain is capable of binding to a cancer cell; and treating the cancer by administering a therapeutically effective dosage of the composition to the subject.
1. A method of treating cancer in a subject, comprising:
providing a composition comprising a polypeptide with at least two domains, wherein the first domain is capable of binding CD3 and the second domain comprises a chlorotoxin peptide and/or a chlorotoxin-like peptide and is capable of binding to a cancer cell;
wherein the composition includes a sequence comprising SEQ ID NO: 9. SEQ ID NO: 10, SEQ ID NO: 11, or SEQ ID NO: 12; and
treating the cancer by administering a therapeutically effective dosage of the composition to the subject.
2. The method of claim 1 , wherein the cancer cell is of neuroectodermal origin.
3. The method of claim 1 , wherein the cancer is glioblastoma multiforme (GBM).
4. The method of claim 1 , wherein the cancer cell comprises peripheral neuroectodermal tumors (PNET).
5. The method of claim 1 , wherein the cancer is medulloblastoma, neuroblastoma, ganglioneuroma, melanoma, adrenal pheochromocytoma, primitive PNET, small cell lung carcinoma, and/or Ewing's sarcoma.
6. The method of claim 1 , wherein the subject is a mammal.
7. The method of claim 1 , wherein the subject is a human.
8. The method of claim 1 , wherein the composition is administered to the subject intravenously.
9. The method of claim 1 , wherein the composition is administered to the subject intracranially.
10. The method of claim 1 , wherein the composition is administered directly to the cancer cells of the subject.
11. The method of claim 1 , wherein the first domain comprises variable heavy (VH) and the variable light (VL) polypeptide chains of an anti-CD3 antibody.
12. The method of claim 11 , wherein the VH polypeptide comprises a sequence having SEQ ID NO: 1 or SEQ ID NO: 2.
13. The method of claim 11 , wherein the VL polypeptide comprises a sequence having SEQ ID NO: 3 or SEQ ID NO: 4.
14. The method of claim 1 , wherein the second domain comprises a polypeptide with a sequence having SEQ ID NO: 6 or SEQ ID NO: 7.
15. The method of claim 1 , wherein the composition further comprises a polypeptide linker between the first and second domain.
16. The method of claim 15 , wherein the polypeptide linker has a sequence Gly-Gly-Gly-Gly-Ser, as set forth in SEQ ID NO 8.