HLA-A2 Specific PLK1 Epitopes for Tumor-Specific CTL Activation

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Solution Overview

Problem

There is a lack of identified epitopes specific for HLA-A2 subtypes that can induce an antigen-specific T cell immune response to the PLK1 protein, which is overexpressed in various cancers, limiting the development of effective tumor vaccines and immunotherapies.

Innovation Solution

The development of specific PLK1-derived epitopes, such as those listed in SEQ ID NOS: 1 to 4, which bind to HLA-A2 subtypes and are recognized by cytotoxic T lymphocytes, are used to induce an antigen-specific T cell immune response, and these epitopes are incorporated into compositions and methods for preventing or treating tumors by administering them to subjects along with antigen presenting cells or cytotoxic T lymphocytes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If PLK1 protein is used as a tumor-target antigen, then tumor-specific T cell immune response can be induced, but the lack of identified HLA-A2-specific epitopes limits the effectiveness

Engineering Contradiction:

Improvetumor-specific T cell immune responseVSAvoidepitope identification

Core Design Contradiction:

ReliabilityVSLoss of information

Solution Approach 1:

The PLK1 protein antigen is segmented into smaller peptide fragments (epitopes) of specific lengths (8-10 amino acids). This segmentation allows identification of specific HLA-A2-binding epitopes (SEQ ID NOS: 1-4) that can be recognized by cytotoxic T lymphocytes, resolving the information loss about which specific regions of PLK1 are immunogenic.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention extracts and identifies specific epitopic regions from the PLK1 protein that have high binding affinity for HLA-A2 molecules. By taking out these critical epitope sequences through bioinformatics analysis and experimental validation, the patent enables targeted use of only the most immunogenic portions of PLK1 for vaccine development.

Inventive Principle:

Principle #2Taking out (Extraction)

2Productivity

If epitopes are selected based on binding affinity to HLA molecules, then T cell activation efficiency is improved, but the complexity of epitope selection and validation increases

Engineering Contradiction:

ImproveT cell activation efficiencyVSAvoidepitope selection process

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent performs preliminary bioinformatics analysis to predict and rank potential epitopes based on their binding affinity to HLA-A2 molecules before experimental validation. This preliminary action filters the large number of possible peptides down to a manageable set of high-probability candidates, reducing the complexity of subsequent experimental work while ensuring high T cell activation efficiency.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The invention replaces extensive experimental screening of all possible peptides with bioinformatics-based prediction algorithms that calculate binding affinity scores. This substitution of computational methods for mechanical/experimental trial-and-error significantly reduces the complexity of epitope selection while maintaining high productivity in identifying effective epitopes.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The identified PLK1-derived epitopes effectively induce antigen-specific T cell immune responses, allowing for the specific targeting and treatment of tumors overexpressing PLK1, including cancers like malignant melanoma and ovarian cancer, by promoting the proliferation of tumor-specific CTLs in vivo.

Implementation Method 1

T cells are activated by recognizing an MHC/peptide antigen complex presented on the surface of an antigen presenting cell (APC) after an antigen-derived peptide fragment (epitope) and a major histocompatibility complex (MHC) are bound to each other

Methodology Applied

Scientific EffectMHC/peptide binding:

Implementation Method 2

T cells specifically responding to an antigen activate another immune response by secreting various cytokines, or are differentiated into killer T cells having a cytotoxic function which recognizes and kills target cells presenting a MHC/peptide antigen complex

Methodology Applied

Scientific EffectCytotoxic cell lysis:

Data Source

PatentUS12054752B2HLA-A2 subtype-specific PLK1-derived epitope inducing antigen-specific t cell immune response to PLK1 protein

Publication Date: 2024.08.06 THE CATHOLIC UNIV OF KOREA IND ACADEMIC COOP FOUND

AI summary

The present invention relates to a HLA-A2 subtype-specific PLK1-derived epitope inducing an antigen-specific T cell immune response to a PLK1 protein. More specifically, a HLA-A2 subtype-specific PLK-1-derived epitope inducing an antigen-specific T cell immune response to a PLK1 protein according to the present invention can provide a CD8+ T cell immune response specific for tumor cells.