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Novel peptides and combination of peptides for use in immunotherapy against hepatocellular carcinoma (HCC) and other cancers

a technology of hepatocellular carcinoma and immunotherapy, which is applied in the field of immunotherapy of cancer, can solve the problems of increasing the risk of cancer development, poor overall prognosis of patients with hcc, and limited therapeutic options for advanced non-resectable h

Inactive Publication Date: 2019-01-03
IMMATICS BIOTECHNOLOGIES GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent is about a new peptide that can trigger an immune response. This peptide is made up of a specific sequence of amino acids. The invention also includes variants of the peptide that can also trigger a response. The peptide is not the full-length polypeptide. The invention also covers a peptide that is 8 to 10 amino acids long. The technical effect of this invention is the use of a specific peptide that can activate T cells and potentially treat disease.

Problems solved by technology

The overall prognosis for patients with HCC is poor.
As a result, healthy liver tissue gets replaced by scar tissue, which increases the risk of cancer development.
Therapeutic options in advanced non-resectable HCC are limited to Sorafenib, a multi-tyrosine kinase inhibitor (Chang et al., 2007; Wilhelm et al., 2004).
Lately, a limited number of immunotherapy trials for HCC have been conducted.
So far, vaccination trials have only shown limited improvements in clinical outcomes.

Method used

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  • Novel peptides and combination of peptides for use in immunotherapy against hepatocellular carcinoma (HCC) and other cancers
  • Novel peptides and combination of peptides for use in immunotherapy against hepatocellular carcinoma (HCC) and other cancers
  • Novel peptides and combination of peptides for use in immunotherapy against hepatocellular carcinoma (HCC) 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

[0543]Patients' tumor tissues were obtained from Universitãtsklinik fũr Allgemeine, Viszeral- and Transplantationschirurgie, Tübingen, Germany; Istituto Nazionale Tumori “Pascale”. Molecular Biology and Viral Oncology Unit, Via Mariano, Naples, Italy; Bio-Options Inc., Brea, Calif., USA; ProteoGenex Inc., Culver City, Calif., USA; Asterand Europe, Royston Herts, United Kingdom. Written informed consents of all patients had been given before surgery. Tissues were shock-frozen immediately after surgery and stored until isolation of TUMAPs at −70° C. or below.

Isolation of HLA Peptides from Tissue Samples

[0544]HLA peptide pools from shock-frozen tissue samples were obtained by immune precipitation from solid tissues according to a slightly modified protocol (Falk, K., 1991; Seeger, F. H. T., 1999) using the HLA-A*02-specific antibody BB7.2, the HLA-A, —B, -C-specific antibody W6 / 32, C...

example 2

Expression Profiling of Genes Encoding the Peptides of the Invention

[0548]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

[0549]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

UV-ligand Exchange / Peptide Binding to HLA-A*02 and HLA-A*24

[0553]Candidate peptides for T cell based therapies according to the present invention were further tested for their MHC binding capacity (affinity). The individual peptide-MHC complexes were produced by UV-ligand exchange, where a UV-sensitive peptide is cleaved upon UV-irradiation, and exchanged with the peptide of interest as analyzed. Only peptide candidates that can effectively bind and stabilize the peptide-receptive MHC molecules prevent dissociation of the MHC complexes. To determine the yield of the exchange reaction, an ELISA was performed based on the detection of the light chain (β2 m) of stabilized MHC complexes. The assay was performed as generally described in Rodenko et al. (Rodenko B, Toebes M, Hadrup S R, van Esch W J, Molenaar A M, Schumacher T N, Ovaa H. Generation of peptide-MHC class I complexes through UV-mediated ligand exchange. Nat Protoc. 2006; 1(3):1120-32.).

[0554]96 well MAXISorp plates (NUNC) we...

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PUM

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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. In particular, the present invention relates to several novel peptide sequences and their variants derived from HLA class I and class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses or as targets for the development of pharmaceutically / immunologically active compounds and cells.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. application Ser. No. 15 / 357,757, filed 21 Nov. 2016, which is a continuation of U.S. application Ser. No. 14 / 975,952 filed 21 Dec. 2015 (now U.S. Pat. No. 10,064,926, issued 4 Sep. 2018) which is incorporated herein by reference in its entirety and that claims priority to 62 / 096,165 filed 23 Dec. 2014, GB 1423016.3 filed 23 Dec. 2014 and GB 1501017.6 filed 21 Jan. 2015.REFERENCE TO SEQUENCE LISTING SUBMITTED AS A COMPLIANT ASCII TEXT FILE (.txt)[0002]A Sequence Listing is submitted herewith as an ASCII compliant text file named “2912919-036005_Sequence_Listing_ST25.txt”, created on Sep. 18, 2018, and having a size of 54,540 bytes as permitted under 37 C.F.R. § 1.821(c). The material in the aforementioned text file is hereby incorporated by reference in its entirety.BACKGROUNDField of the Invention[0003]The present invention relates to peptides, proteins, nucleic acids and cells for use in immunot...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/00G01N33/68C07K14/725A61K38/04C07K7/00C07K7/06C07K7/08C07K14/435A61K35/17C12N15/115C12N5/0783C07K16/18C07K14/74A61K35/12
CPCC07K7/00G01N33/6803C07K2319/40C07K14/435C07K14/70539A61K2039/5154A61K2039/5158C07K14/7051A61K35/17A61K2035/124C07K16/18C12N5/0636C12N15/115C12N2310/16C12N2501/998C07K7/06A61K38/04A61K39/0011C07K2317/70C07K7/08A61K39/00111A61P35/00A61P1/04A61P1/16A61P1/18A61P13/12A61P25/00A61P35/02A61P37/04A61K38/00A61K51/1057
Inventor WEINSCHENK, TONIMAHR, ANDREAFRITSCHE, JENSMULLER, PHILLIPWIEBE, ANITAKUTSCHER, SARA
Owner IMMATICS BIOTECHNOLOGIES GMBH
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