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BR-112018069489-B1 - Uses of a recombinant vector and an immune-inducing agent.

BR112018069489B1BR 112018069489 B1BR112018069489 B1BR 112018069489B1BR-112018069489-B1

Abstract

The present invention relates to a novel immune-inducing agent for the treatment and/or prevention of cancer. Specifically, the present invention relates to an immune-inducing agent comprising, as an active ingredient, at least one polypeptide possessing immune-inducing activity and selected from MRAP2-derived polypeptides and their 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 (6)

  1. 1. USE OF A RECOMBINANT VECTOR comprising a polynucleotide represented by SEQ ID NO: 1 or 7 that encodes a polypeptide consisting of the complete amino acid sequence represented by SEQ ID NO: 2 or 8, respectively, and is capable of expressing said polypeptide in vivo, which has immune-inducing activity, as an active ingredient comprised in an agent, characterized by being for the manufacture of a medicament to induce immunity, wherein the agent is a cancer therapeutic and/or preventive agent that expresses MRAP2.
  2. 2. USE, according to claim 1, characterized in that the agent is an agent for the treatment of antigen-presenting cells.
  3. 3. USE, according to any of claims 1 to 2, characterized by the cancer being leukemia, malignant lymphoma, lung cancer, brain tumor, colon cancer, melanoma, neuroblastoma, pancreatic cancer, stomach cancer, liver cancer, ovarian cancer, esophageal cancer, kidney cancer, 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 derivatives thereof, CpG oligonucleotides, interleukin 12, interleukin 18, interferon-α, interferon-β, interferon-γ, interferon-γ and Flt3 ligand.
  6. 6. USE OF AN IMMUNE-INDUCING AGENT, as defined in any one of claims 1 to 5, characterized in that it is for the manufacture of a medicament for the treatment of antigen-presenting cells.

Description

FIELD OF THE INVENTION [0001] The present invention relates to a novel immune-inducing agent that is useful as a therapeutic and/or preventive agent for cancers and similar diseases. BACKGROUND OF THE INVENTION [0002] 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. [0003] Melanocortin receptor-associated accessory protein 2 (MRAP2) is a type 1 or type 2 transmembrane protein that participates in the control of melanocortin receptor (MCR) activity and functions in energy metabolism in vivo (Non-patent literature 1). Furthermore, MRAP2-deficient mice have been reported to become obese despite not overeating, and it has also been reported in humans that some severely obese patients have a mutation in the MRAP2 gene (Non-patent literature 2). However, there have been no reports that the MRAP2 protein has immune-inducing activity against cancer cells and, therefore, that this protein would be useful for treating and preventing cancers. BACKGROUND LITERATURE OF THE INVENTION [0004] Non-patent literature; Non-patent literature 1: Jackson DS. et al. Front. Neurosci, 9:213(2015); and Non-patent literature 2: Asai M. et al. Science, 341:275-278(2013); BRIEF DESCRIPTION OF THE INVENTION PROBLEMS TO BE SOLVED BY THE INVENTION [0005] One objective of the present invention is to find a novel polypeptide useful as a therapeutic agent and/or preventive agent for cancer and the like, and to provide the use of this polypeptide as an immune-inducing agent. MEANS TO SOLVE THE PROBLEM [0006] 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 Melanocortin 2-associated accessory protein 2 polypeptide (hereinafter referred to as MRAP2) possessing the amino acid sequence represented by SEQ ID NO: 4. Furthermore, based on human, cat, and mouse genes homologous to the canine gene obtained, the present inventors prepared human, cat, and mouse MRAP2 polypeptides possessing the amino acid sequences represented by SEQ ID NOs: 2, 6, and 8. The present inventors have now discovered that these MRAP2 polypeptides are expressed in leukemia, malignant lymphoma, lung cancer, brain tumor, colon cancer, melanoma, neuroblastoma, pancreatic cancer, stomach cancer, liver cancer, ovarian cancer, esophageal cancer, kidney cancer, mast cell tumor, and perianal adenocarcinoma. Furthermore, the present inventors have now discovered that immune cells against MRAP2 can be induced in vivo by administering this MRAP2 protein to living bodies, and that the size of a tumor in living bodies where MRAP2 is expressed can be reduced. In addition, the present inventors have now discovered that a recombinant vector capable of expressing a polynucleotide encoding the MRAP2 polypeptide or a fragment thereof induces an antitumor effect on cancer expressing MRAP2 in vivo. [0007] The present inventors have discovered that the polypeptide MRAP2 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 was realized. [0008] Consequently, the present invention encompasses the following aspects: (1) An immune-inducing agent comprising, as an active ingredient, at least one polypeptide possessing immune-inducing activity and selected from the group consisting 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 on