Targeting PD-L1 on tumor cells
This document relates to materials and methods for treating cancer. For example, this document provides materials and methods for using PD-L1 targeting domains in bispecific chimeric polypeptides, chimeric transmembrane polypeptides, genetically modified viruses, nucleic acid vectors, and/or fusion-inducing cells to treat cancer.
1. A method for treating cancer in a mammal, wherein said method comprises administering a genetically modified virus that expresses a chimeric polypeptide comprising a PD-L1 targeting domain and an effector domain on its surface under conditions wherein the virus is capable of infecting a cancer cell expressing PD-L1, wherein the PD-L1 targeting domain comprises an antibody single-chain variable fragment, wherein the antibody single-chain variable fragment comprises an amino acid sequence encoded by a nucleotide sequence having at least 90% identity to the nucleotide sequence of SEQ ID NO:1.
2. The method of claim 1 , wherein the antibody single-chain variable fragment comprises an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO:1.
3. A method for treating cancer in a mammal, wherein said method comprises administering a genetically modified virus that expresses a chimeric polypeptide comprising a PD-L1 targeting domain and an effector domain on its surface under conditions wherein the virus is capable of infecting a cancer cell expressing PD-L1, wherein the PD-L1 targeting domain comprises an antibody single-chain variable fragment, wherein the antibody single-chain variable fragment comprises an amino acid sequence encoded by a nucleotide sequence having at least 90% identity to the nucleotide sequence of SEQ ID NO:2.
4. The method of claim 3 , wherein the antibody single-chain variable fragment comprises an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO:2.
5. The method of claim 1 , wherein the polypeptide comprising a PD-L1 targeting domain further comprises a hemagglutinin domain.
6. The method of claim 5 , wherein the hemagglutinin domain is selected from the group consisting of: a measles virus H glycoprotein polypeptide, a canine distemper virus H glycoprotein polypeptide, a nipah virus H glycoprotein polypeptide, a rinderpest virus H glycoprotein polypeptide, and a phocine distemper virus H glycoprotein polypeptide.
7. The method of claim 5 , wherein the hemagglutinin domain comprises a modified hemagglutinin domain comprising one or more substitutions, insertions, or deletions, such that the modified hemagglutinin domain exhibits reduced binding to a cellular polypeptide.
8. The method of claim 7 , wherein the cellular polypeptide is selected from the group consisting of: complement regulatory molecule CD46, the signaling lymphocyte activation molecule (SLAM), and Nectin-4.
9. A method for treating cancer in a mammal, wherein said method comprises administering a genetically modified virus that expresses a chimeric polypeptide comprising a PD-L1 targeting domain and an effector domain on its surface under conditions wherein the virus is capable of infecting a cancer cell expressing PD-L1, wherein the effector domain comprises an antibody single-chain variable fragment that binds a CD3 polypeptide, wherein the chimeric polypeptide comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:6.
10. A method for treating cancer in a mammal, wherein said method comprises administering a genetically modified virus that expresses a chimeric polypeptide comprising a PD-L1 targeting domain and an effector domain on its surface under conditions wherein the virus is capable of infecting a cancer cell expressing PD-L1, wherein the effector domain comprises an antibody single-chain variable fragment that binds a CD3 polypeptide, wherein the chimeric polypeptide comprises the amino acid sequence of SEQ ID NO:6.
11. A method for treating cancer in a mammal, wherein said method comprises administering a genetically modified virus that expresses a chimeric polypeptide comprising a PD-L1 targeting domain and an effector domain on its surface under conditions wherein the virus is capable of infecting a cancer cell expressing PD-L1, wherein the effector domain comprises an antibody single-chain variable fragment that binds a CD3 polypeptide, wherein the chimeric polypeptide comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:8.
12. A method for treating cancer in a mammal, wherein said method comprises administering a genetically modified virus that expresses a chimeric polypeptide comprising a PD-L1 targeting domain and an effector domain on its surface under conditions wherein the virus is capable of infecting a cancer cell expressing PD-L1, wherein the effector domain comprises an antibody single-chain variable fragment that binds a CD3 polypeptide, wherein the chimeric polypeptide comprises the amino acid sequence of SEQ ID NO:8.
13. The method of claim 3 , wherein the polypeptide comprising a PD-L1 targeting domain further comprises a hemagglutinin domain.
14. The method of claim 13 , wherein the hemagglutinin domain is selected from the group consisting of: a measles virus H glycoprotein polypeptide, a canine distemper virus H glycoprotein polypeptide, a nipah virus H glycoprotein polypeptide, a rinderpest virus H glycoprotein polypeptide, and a phocine distemper virus H glycoprotein polypeptide.
15. The method of claim 13 , wherein the hemagglutinin domain comprises a modified hemagglutinin domain comprising one or more substitutions, insertions, or deletions, such that the modified hemagglutinin domain exhibits reduced binding to a cellular polypeptide.
16. The method of claim 15 , wherein the cellular polypeptide is selected from the group consisting of: complement regulatory molecule CD46, the signaling lymphocyte activation molecule (SLAM), and Nectin-4.