JPWO2020172189A5 - - Google Patents

Claims (16)

A polypeptide comprising a first domain and a second domain, wherein the first domain comprises a first amino acid sequence that is at least 80% homologous to amino acid positions 48-67 and 110-147 of SEQ ID NO:1 and the second domain has a second amino acid sequence capable of binding to a peptide on tumor cells, said peptide being specific to tumor cells or a non-tumor cell originating from the same tissue as the tumor cells. A polypeptide that is either overexpressed on tumor cells as compared to tumor cells. further comprising a third domain, wherein the third domain is a) an antibody Fc domain;
b) a linker located between the first and second domains, or c) an amino acid sequence capable of binding to a second peptide on tumor cells, wherein the second peptide is specific for tumor cells or is overexpressed on tumor cells as compared to non-tumor cells of the same tissue origin as the tumor cells. 3. The polypeptide of claim 2, wherein the antibody Fc domain comprises a mutation that prevents binding to CD16. 2. The polypeptide of claim 1, wherein the second domain is a single chain variable region fragment derived from an antibody. 2. The polypeptide of claim 1, wherein the polypeptide does not contain an antibody Fc domain. Peptides include ERBB2, CD19, EPCAM, MS4A1, FOLH1, CEACAM5, PMEL, CLEC12A, KDR, EGFR, TAG-72 (tumor-associated glycoprotein 72), disialoganglioside GD2, CD20, CD123, CD33, BCMA, CD38, B7H3 /CD276, GPA33, SSTR2, GPC3, and CDH30. 6. The polypeptide of any one of claims 1-5, wherein the peptide is EGFR. 6. The polypeptide of any one of claims 1-5, wherein the second amino acid sequence comprises SEQ ID NO:14. 6. The polypeptide of any one of claims 1-5, wherein the first amino acid sequence is selected from the group consisting of SEQ ID NO:1 and SEQ ID NO:2. Tumor cells are breast cancer cells, prostate cancer cells, melanoma cells, ovarian cancer cells, gastric cancer cells, glioblastoma cells, neuroblastoma cells, lung cancer cells, lymphoma cells, leukemia cells, colon cancer cells, kidney cells 6. The polypeptide of any one of claims 1-5, which is selected from the group consisting of cancer, pancreatic cancer cells, and hepatocellular carcinoma cells. 6. The polypeptide of any one of claims 1-5, wherein the first amino acid sequence is at least 95% homologous to amino acid positions 48-67 and 110-147 of SEQ ID NO:1. 6. The polypeptide of any one of claims 1-5, wherein the first amino acid sequence is pegylated. 6. The polypeptide of any one of claims 1-5, wherein the first amino acid sequence further comprises PEG-10K, PEG-20K or PEG-40K. A pharmaceutical composition comprising a polypeptide according to any one of claims 1-13 and a pharmaceutically acceptable carrier. 15. A pharmaceutical composition according to claim 14 for use in a method of treating a tumor in a subject. 16. The pharmaceutical composition of claim 15, comprising from about 0.1 μg/Kg to about 50 μg/Kg of the patient's body weight of the polypeptide.