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Predicting immunogenicity of t cell epitopes

a technology of t cell epitopes and immunogenicity, which is applied in the field of methods for predicting t cell epitopes, can solve the problems of not being able to predict no algorithm has been put forth that is capable of predicting with a high degree of certainty, and the accuracy of sequence-based methods is still far behind

Pending Publication Date: 2022-03-24
BIONTECH SE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent is about a type of white blood cell called T helper cells and their role in the immune system. These cells help other cells in the immune system do their job, like making antibodies and fighting disease. The patent also describes how T helper cells become activated and what they do to help the immune system fight disease. The term "immunotherapy" refers to treating or preventing diseases by activating the immune system. The patent describes how this therapy could be used to protect people from tumors or other illnesses.

Problems solved by technology

Yet not every mutation expressed by the tumor can be used as a target for a vaccine.
Thus far no algorithm has been put forth that is capable of predicting with a high degree of certainty which mutations are likely to fulfill all these criteria.
However, the accuracy of those approaches is still far behind the sequence-based methods.
A recent benchmarking study shows, that the available MHC II predictions methods offer a limited accuracy compared to MHC I prediction (H. H. Lin. S. Ray. S. Tongchusak. E. L. Reinherz. V. Brusic. BMC immunology 9, 8 (2008)).
However, to use solely MHC I binding prediction tools for prediction of immunogenicity is misleading, as those tools are trained to predict whether a given peptide has the potential to bind to a given MHC allele.
For that reason, immunogenicity prediction was not very accurate so far, which is mirrored in the low success rates for predicting immunogenicity.
Nevertheless, peptide binding is a necessary but not sufficient condition of T cell epitope recognition, and efficient prediction can dramatically reduce the number of peptides to be tested experimentally.

Method used

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  • Predicting immunogenicity of t cell epitopes
  • Predicting immunogenicity of t cell epitopes
  • Predicting immunogenicity of t cell epitopes

Examples

Experimental program
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Effect test

example 1

ing a Model for Predicting Immunogenicity of T Cell Epitopes

[0270]Previously we explored the immunogenicity of 50 somatic mutations identified in the B16F10 murine melanoma cell line (J. C. Castle et al., Exploiting the mutanome for tumor vaccination. Cancer Research 72, 1081 (2012)). These 50 mutations were selected from a pool of 563 expressed nonsynonymous somatic mutations primarily to maximize MHC class I expression (J. C. Castle et al., Exploiting the mutanome for tumor vaccination. Cancer Research 72, 1081 (2012)) (see also Example 2). For each mutation we predicted the minimal epitope. i.e., the epitope scoring the lowest MHC class I consensus score (Y. Kim et al., Nucleic Acids Research 40, W525 (2012)) (defined here as Mmut) when searching the space of all possible MHC class I alleles, potential epitope lengths and sequence windows (where to position the mutation) (J. C. Castle et al., Exploiting the mutanome for tumor vaccination. Cancer Research 72, 1081 (2012)). Measuri...

example 2

and Methods

[0293]The materials and methods used in Example 1 are described below:

[0294]Animals

[0295]C57BL / 6J and Balb / cJ mice (CRL) were kept in accordance with federal and state policies on animal research at the University of Mainz.

[0296]Cells for Melanoma and Colorectal Murine Tumor Model

[0297]B16F10 melanoma cell line (Product: ATCC CRL-6475. Lot Number: 58078645) and CT26.WT colon carcinoma cell line (Product: ATCC CRL-2638. Lot Number: 58494154) were purchased in 2010 from the American Type Culture Collection. Early (3rd, 4th) passages of cells were used for sequencing experiments. Cells were routinely tested for Mycoplasma. Re-authentication of cells has not been performed since receipt. MZ7-MEL cell line (established January 1988) and an autologous Epstein-Barr vims-transformed B cell line were obtained from Dr. Thomas Wölfel (Department of Medicine. Hematology Oncology. Johannes Gutenberg University).

[0298]Synthetic Peptides

[0299]Peptides were purchased from Jerini Peptide ...

example 3

f a Scheme for Weighing Mutation Scores to Improve Prioritization of Immunogenic Mutations

[0325]RNA that is injected into the cell, once translated and cleaved into short peptides, can be presented on different HLA types within the cell. Therefore it stands to reason that the more HLA types that are predicted to have a low MHC consensus (or similar) score, the more likely a given mutation will be immunogenic since it can potentially be displayed on more than one HLA type in parallel. Thus, weighing mutations by the number of HLA types for which the mutation is classified as HA and / or HB∪HC or even weighing each mutation simply by the number of HLA types that have a low Mmut score may improve immunogenicity ranking. In the most general solution, when we inject a 27mer RNA or peptide into the cell, there is not just the freedom to select the HLA type, but also the length of the peptide and the position of the mutation within this peptide. Therefore, one can scan all possible HLA types...

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Abstract

The present invention relates to methods for predicting T cell epitopes. In particular, the present invention relates to methods for predicting whether modifications in peptides or polypeptides such as tumor-associated neoantigens are immunogenic or not. The methods of the invention are useful, in particular, for the provision of vaccines which are specific for a patient's tumor and thus, in the context of personalized cancer vaccines.

Description

TECHNICAL FIELD OF THE INVENTION[0001]The present invention relates to methods for predicting T cell epitopes. In particular, the present invention relates to methods for predicting whether modifications in peptides or polypeptides such as tumor-associated neoantigens are immunogenic or not. The methods of the invention are useful, in particular, for the provision of vaccines which are specific for a patient's tumor and, thus, in the context of personalized cancer vaccines.BACKGROUND OF THE INVENTION[0002]Personalized cancer vaccines are therapeutic vaccines custom tailored to target tumor-specific mutations that are unique to a given patient. Such a treatment offers great hope for cancer patients as it does not harm healthy cells and has the potential to provide life-long remission. Yet not every mutation expressed by the tumor can be used as a target for a vaccine. In fact, most cancer somatic mutations will not lead to an immune response when vaccinated against (J. C. Castle et a...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): G16B20/20G16B20/00A61K39/00C12Q1/6886
CPCG16B20/20G16B20/00C12Q2600/156C12Q1/6886A61K2039/80A61K39/0011A61P35/00A61K39/00C07K14/00
Inventor SAHIN, UGURTADMOR, ARBEL DAVIDCASTLE, JOHN CHRISTOPHERBOEGEL, SEBASTIANLÖWER, MARTIN
Owner BIONTECH SE
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