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BR-112018069468-B1 - USE OF AN IMMUNE-INDUCING AGENT

BR112018069468B1BR 112018069468 B1BR112018069468 B1BR 112018069468B1BR-112018069468-B1

Abstract

This application relates to a novel immune-inducing agent for the treatment and/or prevention of cancer. Specifically, this application provides an immune-inducing agent comprising, as an active ingredient, at least one polypeptide possessing immune-inducing activity and selected from polypeptides derived from MCEMP1 and its modified forms, or a recombinant vector comprising a polynucleotide encoding the polypeptide and capable of expressing the polypeptide in vivo, and a method for inducing immunity, comprising administering the immune-inducing agent to a subject.

Inventors

  • Takayuki Fujita
  • Fumiyoshi Okano

Assignees

  • TORAY INDUSTRIES, INC

Dates

Publication Date
20260317
Application Date
20170327
Priority Date
20160328

Claims (5)

  1. 1. USE OF AN IMMUNE-INDUCING AGENT, comprising, as an active ingredient, a recombinant vector comprising a polynucleotide represented by SEQ ID NO: 1 or 7 that encodes a polypeptide consisting of a complete sequence of amino acids represented by SEQ ID NO: 2 or 8, respectively, and is capable of expressing said polypeptide in vivo, characterized by being for preparing a medicament to treat and/or prevent cancer that expresses MCEMP1.
  2. 2. USE, according to claim 1, characterized in that the agent is for the treatment of antigen-presenting cells.
  3. 3. USE, according to any of claims 1 to 2, characterized by the cancer being leukemia, myelodysplastic syndrome, osteosarcoma, thymoma, mast cell tumor or perianal adenocarcinoma.
  4. 4. USE, according to any one of claims 1 to 3, characterized in that the agent further comprises an immunostimulant.
  5. 5. USE, according to claim 4, characterized in that the immunostimulant is at least one selected from the group consisting of Freund's incomplete adjuvant, Montanide, Poly IC and its derivatives, CpG oligonucleotides, interleukin 12, interleukin 18, interferon α, interferon β, interferon w, interferon Y and Flt3 ligand.

Description

FIELD OF THE INVENTION [001] The present invention relates to a novel immune-inducing agent that is useful as a therapeutic and/or preventive agent for cancers, or similar diseases. BACKGROUND OF THE INVENTION [002] Cancer is the leading cause of death overall. Currently, the main form of cancer treatment is surgical treatment, which is performed in combination with radiotherapy and chemotherapy. Despite the development of new surgical techniques and the discovery of new antineoplastic agents in recent years, cancer treatment outcomes have not improved, except for some types of cancer. In recent years, for example, cancer antigens recognized by cytotoxic T cells that are reactive to cancer and genes encoding cancer antigens have been identified along with the development of cancer molecular biology and immunology, and expectations for antigen-specific immunotherapy have increased. [003] It has been reported that Mast Cell Expressed Cell Membrane Protein 1 (MCEMP1), a type 2 transmembrane protein, is specifically expressed on the cell membrane in mast cells, suggesting the possibility that the protein participates in mast cell differentiation, immune response, and allergic response (non-patent literature 1). However, there have been no reports that the MCEMP1 protein has immune-inducing activity against cancer cells that would thus be useful for treating and preventing cancers. BACKGROUND LITERATURE OF THE INVENTION [004] Non-patent literature:- Non-patent literature 1: Kang Li. et al. Genomics,86:68- 75(2005) BRIEF DESCRIPTION OF THE INVENTION PROBLEMS TO BE SOLVED BY THE INVENTION [005] One objective of the present invention is to find a novel polypeptide useful as a therapeutic and/or preventive agent for cancer and to provide the use of this polypeptide as an immune-inducing agent. MEANS FOR SOLVING THE PROBLEMS [006] The present inventors conducted intensive studies, and as a result, have now obtained a cDNA that encodes a protein that binds to an antibody present in sera from living bodies bearing cancer by the SEREX method using a cDNA library derived from canine testis along with sera from dogs with leukemia. Based on cDNA, the present inventors prepared a canine Mast Cell Expressed Cell Membrane Protein 1 polypeptide (hereinafter referred to as MCEMP1) possessing the amino acid sequence represented by SEQ ID NO: 4. Furthermore, based on human, cat, and mouse genes homologous to the obtained canine gene, the present inventors prepared human, cat, and mouse MCEMP1 polypeptides possessing the amino acid sequences represented by SEQ ID NOs: 2, 6, and 8. The present inventors have now discovered that these MCEMP1 polypeptides are specifically expressed in leukemia, myelodysplastic syndrome, osteosarcoma, thymoma, mastocytoma, and perianal adenocarcinoma. In addition, they have now further discovered that immune cells against MCEMP1 can be induced in vivo by administering these MCEMP1s to living bodies, and that the size of a tumor in living bodies where MCEMP1 is expressed can be reduced. Furthermore, the present inventors have now discovered that a recombinant vector capable of expressing a polynucleotide encoding the MCEMP1 polypeptide or a fragment thereof induces an antitumor effect in MCEMP1-expressing cancer in vivo. [007] The present inventors have now discovered that the polypeptide MCEMP1 is presented by an antigen-presenting cell and has an ability (also referred to as “immunity-inducing activity”) to activate and proliferate a polypeptide-specific cytotoxic T cell; such that the polypeptide is useful for treating and/or preventing cancers due to this ability; and that the antigen-presenting cell, which was in contact with the polypeptide, and the T cell, which was in contact with the antigen-presenting cell, are useful for treating and/or preventing cancers. Based on the results, the present invention has been realized. [008] Consequently, the present invention includes the following features (1) to (11):(1) An immune-inducing agent comprising, as an active ingredient, at least one polypeptide possessing immune-inducing activity and selected from any of the following polypeptides (a) to (d), or a recombinant vector comprising a polynucleotide encoding the polypeptide and capable of expressing said polypeptide in vivo:(a) a polypeptide consisting of 7 or more consecutive amino acids or a complete sequence in the amino acid sequence represented by SEQ ID NO: 2, 4, 6 or 8 in the Sequence Listing;(b) a polypeptide consisting of an amino acid sequence obtained by deletion, substitution or addition of one or more amino acids in the amino acid sequence represented by SEQ ID NO: 2, 4, 6 or 8 in the Sequence Listing;(c) a polypeptide consisting of an amino acid sequence possessing a sequence identity of 90% or more with the amino acid sequence represented by SEQ ID NO: 2, 4, 6 or 8 in the Sequence Listing; (d) a polypeptide comprising any of the polypeptides from (a) to (c) as a partial sequence; (2) T