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US-12622956-B2 - Methods and vaccines for inducing immune responses to multiple different MHC molecules

US12622956B2US 12622956 B2US12622956 B2US 12622956B2US-12622956-B2

Abstract

This document provides methods and materials relating to isolated polypeptides, polypeptide preparations, vaccine preparations (e.g., anti-cancer vaccine preparations), and methods for vaccinating mammals. For example, polypeptides (e.g., CMV, MUC1, HER2, Mesothelin (MESO), TRAG-3, or CALR polypeptides) having the ability to be processed into different polypeptides such that the processed polypeptides as a group are capable of being presented by different MHC molecules present in a particular mammalian population are provided.

Inventors

  • Dustin B. McCurry
  • Peter A. Cohen
  • Latha B. Pathangey
  • Sandra J. Gendler
  • MARY L DISIS

Assignees

  • MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH
  • UNIVERSITY OF WASHINGTON

Dates

Publication Date
20260512
Application Date
20220824

Claims (20)

  1. 1 . An isolated polypeptide, wherein the amino acid sequence of said polypeptide is as set forth in any one of SEQ ID NOs:1-58, and wherein said polypeptide is amidated at the C-terminus.
  2. 2 . An isolated polypeptide, wherein the amino acid sequence of said polypeptide is as set forth in any one of SEQ ID NOs:1-58, and wherein said polypeptide is acetylated at the N-terminus.
  3. 3 . A composition comprising at least one isolated polypeptide and an adjuvant, wherein the amino acid sequence of said at least one polypeptide is as set forth in any one of SEQ ID NOs:1-58, and wherein said adjuvant is CpG, aluminum sulfate, aluminum phosphate, MF59, Pam3CSK4, LPS, polyIC, imiquimod, or R848.
  4. 4 . The composition of claim 3 , wherein said polypeptide is amidated at the C-terminus and/or acetylated at the N-terminus.
  5. 5 . The composition of claim 3 , wherein said adjuvant is aluminum sulfate or aluminum phosphate.
  6. 6 . A method of treating cancer or a precancerous condition in a mammal, wherein said method comprises administering to said mammal a composition comprising an adjuvant and at least one polypeptide, wherein the amino acid sequence of said polypeptide is as set forth in any one of SEQ ID NOs:1-58, and wherein said adjuvant is CpG, aluminum sulfate, aluminum phosphate, or MF59.
  7. 7 . The method of claim 6 , wherein said mammal is a human.
  8. 8 . The method of claim 6 , wherein said method comprises treating said cancer, and wherein said cancer is breast cancer, pancreatic cancer, ovarian cancer, stomach cancer, lung cancer, colon cancer, multiple myeloma, leukemia, brain cancer, or melanoma cancer.
  9. 9 . The method of claim 6 , wherein said method comprises treating said precancerous condition, and wherein said precancerous condition is primary myelofibrosis, essential thrombocythemia, or polycythemia vera.
  10. 10 . The method of claim 6 , wherein said adjuvant is aluminum sulfate or aluminum phosphate.
  11. 11 . The method of claim 6 , wherein said polypeptide is amidated at the C-terminus and/or acetylated at the N-terminus.
  12. 12 . A vaccine comprising an adjuvant and at least one polypeptide, wherein the amino acid sequence of said polypeptide is as set forth in any one of SEQ ID NOs:1-58, and wherein said adjuvant is CpG, aluminum sulfate, aluminum phosphate, or MF59.
  13. 13 . The vaccine of claim 12 , wherein said adjuvant is CpG or MF59.
  14. 14 . The vaccine of claim 12 , wherein said polypeptide is amidated at the C-terminus and/or acetylated at the N-terminus.
  15. 15 . A method of inducing an immune response against at least one polypeptide, wherein the sequence of said polypeptide is as set forth in any one of SEQ ID NOs:1-58, wherein said method comprises administering a composition comprising said polypeptide and an adjuvant to a mammal in an amount effective to induce an immune response against said polypeptide, wherein said adjuvant is CpG, aluminum sulfate, aluminum phosphate, or MF59.
  16. 16 . The method of claim 15 , wherein said adjuvant is aluminum sulfate or aluminum phosphate.
  17. 17 . The method of claim 15 , wherein said adjuvant is CpG or MF59.
  18. 18 . The method of claim 15 , wherein said polypeptide is amidated at the C-terminus and/or acetylated at the N-terminus.
  19. 19 . A method of treating cancer or a precancerous condition in a mammal, wherein said method comprises contacting T-cells obtained from said mammal with at least one polypeptide set forth in any one of SEQ ID NOs:1-58 to activate said T-cells, and administering said activated T-cells to said mammal.
  20. 20 . The method of claim 19 , wherein said mammal is a human.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. application Ser. No. 15/781,393, filed Jun. 4, 2018, which is a National Stage Application under 35 U.S.C. § 371 that claims the benefit of Application Serial No. PCT/US2016/064749, filed Dec. 2, 2016, which also claims the benefit of U.S. Provisional Application Ser. No. 62/263,256, filed Dec. 4, 2015. The disclosures of the prior applications are considered part of (and are incorporated by reference in) the disclosure of this application. STATEMENT AS TO FEDERALLY SPONSORED RESEARCH This invention was made with government support under CA136632 and CA102701 awarded by the National Institutes of Health. The federal government has certain rights in the invention. SEQUENCE LISTING This application contains a Sequence Listing that has been submitted electronically as an XML file named 07039-1505002sub_SL.xml. The XML file, created on Oct. 1, 2025, is 101,504 bytes in size. The material in the XML file is hereby incorporated by reference in its entirety. 1. BACKGROUND 1. Technical Field This document provides methods and materials relating to isolated polypeptides, polypeptide preparations, vaccine preparations (e.g., anti-cancer vaccine preparations), and methods for vaccinating mammals. For example, this document provides polypeptides having the ability to be processed into a collection of different polypeptides such that the polypeptides of the collection are capable of being presented by different major histocompatibility complex (MHC) molecules present in a particular mammalian population. 2. Background Information Polypeptide-based vaccines use polypeptide sequences derived from target proteins as epitopes to provoke an immune reaction. These vaccines are a result of an improved understanding of the molecular basis of epitope recognition, thereby permitting the development of rationally designed, epitope-specific vaccines based on motifs demonstrated to bind to MHC molecules. SUMMARY This document provides methods and materials relating to isolated polypeptides, polypeptide preparations, vaccine preparations (e.g., anti-cancer vaccine preparations), and methods for vaccinating mammals. For example, this document provides polypeptides (e.g., CMV pp65, MUC1, HER2, Mesothelin (MESO), TRAG-3, or Calreticulin (CALR) polypeptides) having the ability to be processed into different polypeptides such that the processed polypeptides as a group are capable of being presented by different MHC molecules present in a particular mammalian population. In some cases, the group of processed polypeptides can bind to at least 85 percent (e.g., at least about 87, 90, of 95 percent) of the MHC molecules present in a particular mammalian population such as humans. This document also provides methods and materials (e.g., vaccine preparations) for treating cancer. For example, the vaccine preparations provided herein can include one or more of the MUC1, HER2, MESO, TRAG-3, or CALR polypeptides provided herein (see, e.g., Table 1) and can have the ability to induce a protective or therapeutic immune response within a mammal (e.g., a human). As described herein, polypeptides ranging from about 18 to about 55 (e.g., about 18 to about 50, about 20 to about 50, about 25 to about 50, about 30 to about 50, about 18 to about 45, about 18 to about 40, about 18 to about 35, about 20 to about 45, about 25 to about 40, or about 30 to about 35) amino acid residues in length were identified, produced, and confirmed to have the ability to induce immune responses in the context of multiple different MHC molecules. The identification of these polypeptides can be used to aid in understanding immune processes and can be used to generate anti-cancer vaccine preparations. In general, one aspect of this document features an isolated polypeptide, wherein the amino acid sequence of the polypeptide is as set forth in any one of SEQ ID NOs:1-58. In another aspect, this document features a composition comprising, or consisting essentially of, at least one isolated polypeptide selected from the group consisting of SEQ ID NOs:1-58. The composition can further comprise an adjuvant. In another aspect, this document features a method of treating cancer or a precancerous condition in a mammal. The method comprises, or consists essentially of, administering to the mammal a composition comprising an adjuvant and at least one polypeptide, wherein the amino acid sequence of the polypeptide is as set forth in any one of SEQ ID NOs:1-58. The mammal can be a human. The cancer can be breast cancer, pancreatic cancer, ovarian cancer, stomach cancer, lung cancer, colon cancer, multiple myeloma, leukemia, brain cancer, or melanoma cancer. The precancerous condition can be primary myelofibrosis, essential thrombocythemia or polycythemia vera. The adjuvant can be CpG, aluminum sulfate, aluminum phosphate, MF59, Pam3CSK4, LPS, polyIC, imiquimod, or R848. In another aspect, this document featur