JP-7856604-B2 - Common neoantigen

Inventors

• エドワード・エフ・フリッチ
• ニア・ハコーヘン
• マイケル・スティーヴン・ルーニー
• サチェット・アショク・シュクラ
• キャサリン・ジェイ・ウー
• パヴァン・バチレディー
• ジン・スン

Assignees

• ザ・ブロード・インスティテュート・インコーポレイテッド
• デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド
• ザ ジェネラル ホスピタル コーポレイション

Dates

Publication Date

20260511

Application Date

20230517

Priority Date

20150520

Claims (14)

1. A composition that is an immunogenic composition or vaccine composition for use in the treatment or prevention of chromophobe cell carcinoma of the kidney (KICH), the following: (a) Recombinant or synthetic neoantigen peptides that bind to HLA proteins; (b) Polynucleotides encoding recombinant neoantigen peptides; (c) Antigen-presenting cells (APCs) including (a) or (b); (d) T cells stimulated with an APC comprising (a) or (b); or (e) a T cell receptor (TCR) that binds to an MHC:peptide complex comprising a tumor-specific neoepitope of recombinant or synthetic neoantigen peptide that binds to an HLA protein. Includes, Neoantigen peptides contain tumor-specific neoepitopes of 8-10 amino acids in length, which include amino acid sequences encoded in the downstream sequence of a frameshift mutation in a gene. The gene in question is UBR5, and its neoantigen peptides are KNSPCCQKK (SEQ ID NO: 30664), KLRVQNQGH (SEQ ID NO: 30665), RVQNQGHLL (SEQ ID NO: 30666), VQNQGHHLLM (SEQ ID NO: 30667), LRVQNQGHL (SEQ ID NO: 30668), NQGHHLLMIL (SEQ ID NO: 30669), and MQNRQKKKGK (SEQ ID NO: 30670). The composition is a peptide comprising an amino acid sequence selected from the group consisting of KGKNSPCCQK (SEQ ID NO: 30671), KLRVQNQGHL (SEQ ID NO: 30672), RVQNQGHLLM (SEQ ID NO: 30673), LRVQNQGHLL (SEQ ID NO: 30674), VQNQGHLLMI (SEQ ID NO: 30675), and NQGHLLMILL (SEQ ID NO: 30676).
2. The composition according to claim 1, wherein the gene is UBR5 and the frameshift is the K2120fs mutation.
3. The composition according to claim 1, wherein the gene is UBR5 and contains the c. 6360delA mutation.
4. The composition according to claim 1, wherein the tumor-specific neoepitope is (a) encoded by a gene of a human cancer cell, (b) expressed by a human cancer cell, (c) not expressed by a gene of a human non-cancer cell, and (d) not encoded by a gene of a non-cancer cell.
5. A vaccine, the composition according to claim 1.
6. The composition according to claim 1, wherein the polynucleotide encoding the recombinant neoantigen peptide is DNA.
7. The composition according to claim 1, wherein the polynucleotide encoding the recombinant neoantigen peptide is messenger RNA (mRNA).
8. A pharmaceutical composition for use in the treatment or prevention of KICH in a human subject as needed , comprising the composition according to claim 1, and a pharmaceutically acceptable carrier, excipient, or diluent.
9. The pharmaceutical composition according to claim 8 , further comprising an adjuvant.
10. Use of the pharmaceutical composition according to claim 9 in the manufacture of a pharmaceutical for treating or preventing KICH in human subjects who require it.
11. The use according to claim 10 , wherein the pharmaceutical composition is administered prophylactically.
12. The use according to claim 10 , wherein the human subject is at risk of developing KICH.
13. The pharmaceutical composition according to claim 8 , administered prophylactically.
14. The pharmaceutical composition according to claim 8 , wherein human subjects are at risk of developing KICH.

Description

Related Applications and References This application claims priority and benefit of U.S. Provisional Application No. 62/179,877 filed on 20 May 2015 and U.S. Provisional Application No. 62/389,377 filed on 23 February 2016. The aforementioned application, and all cited documents in the application or its examination procedures ("Application Citations"), and all documents cited or referenced in the Application Citations, and all documents cited or referenced herein ("Specified Citations"), and all documents cited or referenced in the Specified Citations, together with any manufacturer's instructions, descriptions, product specifications, and product sheets relating to any product mentioned herein or in any document referred herein, are incorporated herein by reference and may be used in practice of the present invention. More specifically, all referenced documents are incorporated by reference to the same extent as each individual document is specifically and individually indicated as to be incorporated by reference. This invention relates to a method and composition for treating neoplasms (e.g., tumors) using, in particular, at least one neoantigen peptide suitable for treating a substantial proportion of subjects in a population affected by cancer. Approximately 1.6 million Americans are diagnosed with neoplasms each year, and in 2013, it was estimated that around 580,000 people in the U.S. would die from this disease. In recent decades, the detection, diagnosis, and treatment of neoplasms have improved dramatically, leading to significantly higher survival rates for many types of neoplasms. However, only about 60% of those diagnosed with neoplasms are still alive five years after starting treatment, making neoplasms the second leading cause of death in the United States. Currently, there are numerous existing cancer therapies, including ablation techniques (e.g., surgical procedures, cryo/thermal treatment, ultrasound, radiofrequency, and radiation) and chemical techniques (e.g., pharmaceuticals, cytotoxic/chemotherapeutic agents, monoclonal antibodies, and various combinations thereof). Unfortunately, these treatments often carry serious risks, toxic side effects, and extremely high costs, in addition to their uncertain effectiveness. To aid in understanding this invention, several terms and phrases are defined herein. Unless otherwise stated or made clear from the context, the term “about” as used herein is understood to mean within the normal tolerances in the art, for example, within two standard deviations of the mean. “About” can be understood to mean within 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the stated value. Unless otherwise made clear from the context, all numerical values provided herein are modified by the term “about.” Unless specifically stated or evident from the context, the term "or" is understood to be inclusive when used herein. Unless specifically stated or evident from the context, the terms "a,""an," and "the" are understood to be singular or plural when used herein. All gene nomenclature symbols refer to genes commonly known in the relevant technical field. Gene nomenclature symbols may also be referenced by the HUGO Gene Nomenclature Committee (HGNC). Any reference to this gene nomenclature refers to the entire gene or a variant of this gene. The HUGO Gene Nomenclature Committee is involved in providing human gene nomenclature guidelines and approving new and unique human gene names and symbols. All human gene names and symbols can be searched on the HGNC website, www.genenames.org, and the guidelines for creating these names and symbols are available on this website (www.genenames.org/guidelines). "Drug" means any small molecule chemical compound, antibody, nucleic acid molecule, polypeptide, or fragment thereof. "To improve" means to reduce, suppress, weaken, decrease, halt, or stabilize the onset or progression of a disease (e.g., neoplasm, tumor, etc.). "Modification" means a change (increase or decrease) in the expression level or activity of a gene or polypeptide as detected by standard methods known in the art, such as those described herein. As used herein, modification includes changes of 10% in expression level, preferably 25% in expression level, more preferably 40%, and most preferably 50% or more. An "analog" refers to a molecule that is not identical but possesses similar functional or structural characteristics. For example, a tumor-specific neoantigen polypeptide analog retains the biological activity of the corresponding naturally occurring tumor-specific neoantigen polypeptide while possessing specific biochemical modifications that enhance the analog's function compared to the naturally occurring polypeptide. Such biochemical modifications may increase the analog's protease resistance, membrane permeability, or half-life, for example, without altering ligand binding. Analogies may include