Peptide vaccines

A technology of polypeptide antigens and amino acids, applied in the field of polypeptides and vaccines

Pending Publication Date: 2021-08-31
特雷斯生物有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Scaling up HLA-specific cancer vaccines to large populations is currently not feasible using existing technologies

Method used

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Examples

Experimental program
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Effect test

example 1

[0587] Example 1 HLA epitope binding prediction method and verification

[0588] Prediction of binding between specific HLAs and epitopes (9mer peptides) was based on the ImmunoEpitope Database tool for epitope prediction (www.iedb.org).

[0589] The HLA I epitope binding prediction process was validated by comparison with HLA I epitope pairs determined by laboratory experiments. Datasets of HLA I epitope pairs reported in peer-reviewed publications or public immunology databases were compiled.

[0590] The rate of agreement with the experimentally determined data set (Table 2) was determined. Binding HLA I epitope pairs for the dataset were correctly predicted with 93% probability. Coincidentally, non-binding HLA I epitope pairs were also predicted correctly with a probability of 93%.

[0591] Table 2 Analytical specificity and sensitivity of HLA epitope binding prediction methods

[0592]

[0593] The accuracy of predicting multiple HLA binding epitopes was also det...

example 2

[0597] Example 2 Epitope Presentation of Multiple HLAs Predicts Cytotoxic T Lymphocyte (CTL) Response

[0598] This study investigated whether an individual's presentation of one or more epitopes of a polypeptide antigen by one or more HLA class I molecules is predictive of a CTL response.

[0599] The study was performed by a retrospective analysis of 6 clinical trials conducted in 71 cancer patients and 9 HIV-infected patients (Table 4)1-7. Patients from these studies were treated with HPV vaccines, three different NY-ESO-1-specific cancer vaccines, an HIV-1 vaccine, and a CTLA-4-specific monoclonal antibody (ipilimmab), the Antibodies shown to reactivate CTLs against NY-ESO-1 antigen in melanoma patients. All of these clinical trials measure antigen-specific CD8+ CTL responses (immunogenicity) in study subjects after vaccination. In some cases, a correlation between CTL response and clinical response was reported.

[0600] No patients were excluded from the retrospecti...

example 3

[0612] Example 3 Retrospective Validation of ≥1 PEPI3+ Threshold as a New Biomarker for PEPI Test

[0613] In a retrospective analysis, a test cohort of 81 datasets from 51 patients was used to validate a ≥1 PEPI3+ threshold to predict antigen-specific CD8+ T cell or CTL responses. For each data set in the test cohort, it was determined whether a > 1 PEPI3+ threshold (at least one antigen-derived epitope presented by at least three class I HLAs of the individual) was met. This was compared to experimentally measured CD8+ T cell responses (CTL responses) reported in clinical trials (Table 7).

[0614] A retrospective validation demonstrated that the PEPI3+ peptide induces a CD8+ T cell response (CTL response) in an individual with a probability of 84%. 84% is the same value as determined in the analytical validation of the PEPI3+ prediction that the epitope is bound to at least 3 HLAs of the individual (Table 3). These data provide strong evidence that PEPI induces an immun...

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Abstract

The disclosure relates to polypeptides and pharmaceutical compositions comprising polypeptides that find use in the prevention or treatment of cancer, in particular gastric cancer, lung cancer, melanoma and bladder cancer. The disclosure also relates to methods of inducing a cytotoxic T cell response in a subject or treating cancer by administering the pharmaceutical compositions comprising the peptides, and companion diagnostic methods of identifying subjects for treatment. The peptides comprise T cell epitopes that are immunogenic in a high percentage of patients.

Description

technical field [0001] The present disclosure relates to polypeptides and vaccines for the prevention or treatment of cancer, particularly cancers expressing certain antigens expressed in gastric cancer, lung cancer, melanoma and bladder cancer. Background technique [0002] Cancer is killing millions of people around the world because existing medicines cannot effectively prevent or treat it. Current checkpoint inhibitor immunotherapies that reactivate existing immune responses could provide clinical benefit to a subset of cancer patients. Current cancer vaccines that induce new immune responses are poorly immunogenic and fail to benefit most patients. [0003] A recent analysis of 63,220 unique tumors demonstrated the need to generate cancer vaccines specifically for each patient due to extensive inter-individual tumor genomic heterogeneity (Hartmaier et al. Genome Medicine 2017 9:16). Extending HLA-specific cancer vaccines to large populations is currently not feasible ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00A61P35/00G01N33/50G01N33/569
CPCA61K39/0011A61K39/001184A61K39/001189A61K39/00115A61K2039/70A61K39/001166A61P35/00A61K2039/828G01N33/56977G01N2800/52C07K14/4748A61P1/00A61K39/001186A61K45/06A61K2039/545
Inventor 朱丽安娜·利兹维奇列文特·莫尔纳埃尼科·托克约瑟夫·托特奥索利亚·洛林茨若尔特·塞斯佐夫斯基埃斯特·索莫吉卡塔林·潘蒂亚莫妮卡·梅格耶西
Owner 特雷斯生物有限公司
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