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Peptides, combination of peptides, and cell based medicaments for use in immunotherapy against urinary bladder cancer and other cancers

a technology of immunotherapy and peptides, applied in the field of peptides, proteins, nucleic acids and cells for use in immunotherapy of cancer, can solve the problems of difficult treatment of patients who fail to respond to bcg therapy, death of immunocompromised patients, and inability to respond to bcg treatmen

Inactive Publication Date: 2019-10-31
IMMATICS BIOTECHNOLOGIES GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent text describes a method of making peptides that can be used to diagnose cancer and other diseases. These peptides can be added to tissue samples to help with diagnosis and can also be used as biomarkers for urinary bladder cancer. The peptides can be added to the tissue sample to increase their stability or solubility. Overall, this method can help with the diagnosis and classification of diseased tissues.

Problems solved by technology

BCG treatment is in general well tolerated by patients but can be fatal especially by the immunocompromised patients.
The treatment of patients who failed the BCG therapy is challenging.
The patients who failed the BCG treatment are at high risk for developing of muscle-invasive disease.
In general, the treatment of advanced bladder cancer with muscle invasion known as muscle-invasive bladder carcinoma (MIBC) or metastatic bladder cancer is challenging and remained substantially unchanged over the last few decades.
Nowadays available options for treatment of progressed bladder cancer are insufficiently effective.
The adjuvant application of chemotherapy by the treatment of MIBC is limited by the high surgical complication rate after radical cystectomy.
Furthermore, patients with impaired renal function are ineligible for treatment with cisplatin.
The development of molecularly targeted therapies remains challenging due to high degree of genetic diversity of bladder cancer.
Since the constitutive expression of HLA class II molecules is usually limited to immune cells, the possibility of isolating class II peptides directly from primary tumors was previously not considered possible.
However, the identification of genes over-expressed in tumor tissues or human tumor cell lines, or selectively expressed in such tissues or cell lines, does not provide precise information as to the use of the antigens being transcribed from these genes in an immune therapy.

Method used

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  • Peptides, combination of peptides, and cell based medicaments for use in immunotherapy against urinary bladder cancer and other cancers
  • Peptides, combination of peptides, and cell based medicaments for use in immunotherapy against urinary bladder cancer and other cancers
  • Peptides, combination of peptides, and cell based medicaments for use in immunotherapy against urinary bladder cancer and other cancers

Examples

Experimental program
Comparison scheme
Effect test

example 1

Identification and Quantitation of Tumor Associated Peptides Presented on the Cell Surface

Tissue Samples

[0344]Patients' tumor tissues were obtained from: Asterand (Detroit, Mich., USA & Royston, Herts, UK); Geneticist Inc. (Glendale, Calif., USA); ProteoGenex Inc. (Culver City, Calif., USA); Tissue Solutions Ltd (Glasgow, UK); and University Hospital Tübingen (Tübingen, Germany)

[0345]Normal tissues were obtained from

Asterand (Detroit, Mich., USA & Royston, Herts, UK); Bio-Options Inc. (Brea, Calif., USA); BioServe (Beltsville, Md., USA); Blutspendezentrale, Zentrum für Klinische Transfusionsmedizin, Tübingen; Capital BioScience Inc. (Rockville, Md., USA); Geneticist Inc. (Glendale, Calif., USA); Kyoto Prefectural University of Medicine (KPUM) (Kyoto, Japan); ProteoGenex Inc. (Culver City, Calif., USA); Tissue Solutions Ltd (Glasgow, UK); University Hospital Geneva (Geneva, Switzerland); University Hospital Heidelberg (Heidelberg, Germany); University Hospital Munich (Munich, Germany...

example 2

Expression Profiling of Genes Encoding the Peptides of the Invention

[0350]Over-presentation or specific presentation of a peptide on tumor cells compared to normal cells is sufficient for its usefulness in immunotherapy, and some peptides are tumor-specific despite their source protein occurring also in normal tissues. Still, mRNA expression profiling adds an additional level of safety in selection of peptide targets for immunotherapies. Especially for therapeutic options with high safety risks, such as affinity-matured TCRs, the ideal target peptide will be derived from a protein that is unique to the tumor and not found on normal tissues.

RNA Sources and Preparation

[0351]Surgically removed tissue specimens were provided as indicated above (see Example 1) after written informed consent had been obtained from each patient. Tumor tissue specimens were snap-frozen immediately after surgery and later homogenized with mortar and pestle under liquid nitrogen. Total RNA was prepared from t...

example 3

In Vitro Immunogenicity for MHC Class I Presented Peptides

[0356]In order to obtain information regarding the immunogenicity of the TUMAPs of the present invention, the inventors performed investigations using an in vitro T-cell priming assay based on repeated stimulations of CD8+ T cells with artificial antigen presenting cells (aAPCs) loaded with peptide / MHC complexes and anti-CD28 antibody. This way the inventors could show immunogenicity for HLA-A*0201 restricted TUMAPs of the invention, demonstrating that these peptides are T-cell epitopes against which CD8+ precursor T cells exist in humans (Table 10).

In Vitro Priming of CD8+ T Cells

[0357]In order to perform in vitro stimulations by artificial antigen presenting cells loaded with peptide-MHC complex (pMHC) and anti-CD28 antibody, the inventors first isolated CD8+ T cells from fresh HLA-A*02 leukapheresis products via positive selection using CD8 microbeads (Miltenyi Biotec, Bergisch-Gladbach, Germany) of healthy donors obtained...

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Abstract

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a Continuation of U.S. patent application Ser. No. 15 / 445,461, filed 28 Feb. 2017, which claims the benefit of U.S. Provisional Application Ser. No. 62 / 302,010, filed 1 Mar. 2016, and Great Britain Application No. 1603568.5, filed 1 Mar. 2016, the content of each of these applications is herein incorporated by reference in their entirety.[0002]This application also is related to PCT / EP2017 / 054559 filed 28 Feb. 2017, the content of which is incorporated herein by reference in its entirety.REFERENCE TO SEQUENCE LISTING SUBMITTED AS A COMPLIANT ASCII TEXT FILE (.TXT)[0003]Pursuant to the EFS-Web legal framework and 37 CFR §§ 1.821-825 (see MPEP § 2442.03(a)), a Sequence Listing in the form of an ASCII-compliant text file (entitled “2912919-063002_Sequence_Listing_ST25.txt” created on 27 Jun. 2019, and 32,328 bytes in size) is submitted concurrently with the instant application, and the entire contents of the Sequence List...

Claims

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Application Information

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IPC IPC(8): C07K7/08A61K35/17G01N33/68C07K16/18C12N15/115A61K39/00C07K14/47C07K14/725C07K7/06
CPCA61K2039/80C07K14/7051C07K16/18A61K2039/868A61K39/0011A61K2039/836A61K35/17G01N33/6893A61K2039/844C12N15/115A61K2039/884C07K7/06C07K2319/00A61K2039/852A61K2039/892A61K2039/86A61K2039/82C07K14/4748C12N2310/16A61K2039/804A61K2039/812A61K2039/828A61K2035/124G01N2800/52A61K2039/5154A61K2039/876C07K7/08C12N5/0638G01N33/57484A61P35/00A61K39/4611A61K39/4637A61K39/001154A61K39/4644A61K39/001102A61P37/02A61K38/00A61P37/04
Inventor MAHR, ANDREAWEINSCHENK, TONISONG, COLETTESCHOOR, OLIVERFRITSCHE, JENSSINGH, HARPREET
Owner IMMATICS BIOTECHNOLOGIES GMBH
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