HPV16 Immunogenic Epitopes for HLA-Restricted T-Cell Targeting

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Solution Overview

Problem

Current therapeutic strategies for HPV16-associated cancers, particularly HPV+ HNSCC, are limited by low genome integration rates and inefficient immune targeting, leading to T-cell dysfunction and resistance to existing immunotherapies.

Innovation Solution

Identification of novel immunogenic epitopes from HPV16 E2, E6, and E7 antigens restricted by common HLA alleles, combined with immune checkpoint inhibitors like PD-1 and IDO-1, to enhance T-cell targeting and overcome dysfunction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional immunotherapies are used for HPV16-associated cancers, then treatment is provided, but T-cell dysfunction and resistance occur due to low genome integration rates and inefficient immune targeting

Engineering Contradiction:

Improveimmune targeting efficiencyVSAvoidT-cell dysfunction

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent segments the immune response by identifying and targeting specific epitopes (immunogenic regions) within the HPV16 E2, E6, and E7 antigens. This segmentation allows for precise T-cell targeting against specific viral proteins, overcoming the inefficiency of conventional broad-spectrum immunotherapies and addressing T-cell dysfunction through epitope-specific activation

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent changes the parameter of immune recognition by identifying epitopes restricted by common HLA alleles (HLA-A*02:01, HLA-A*11:01, HLA-B*08:01). This parameter change ensures that the immunotherapy can effectively target a broader population of patients with varying HLA types, improving immune targeting efficiency while overcoming resistance

Inventive Principle:

Principle #35Parameter changes

2Reliability

If therapeutic vaccines targeting viral neo-epitopes are developed, then T-cell targeting is enhanced, but the complexity of identifying HLA-restricted epitopes increases

Engineering Contradiction:

ImproveT-cell targetingVSAvoidepitope identification process

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies universality by identifying epitopes restricted by common HLA alleles that are present in a large proportion of the population. These multi-functional epitopes can be targeted across different patient groups, simplifying the overall therapeutic approach while maintaining effective T-cell targeting without requiring highly complex personalized epitope mapping for each patient

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Productivity

If immune checkpoint inhibitors are combined with epitope-specific vaccines, then T-cell cytotoxicity is enhanced, but the treatment protocol complexity increases

Engineering Contradiction:

ImproveT-cell cytotoxicityVSAvoidtreatment protocol

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent merges two therapeutic approaches: epitope-specific vaccination (targeting HPV16 E2, E6, E7 antigens) and immune checkpoint inhibition (anti-PD-1/PD-L1 antibodies). This combination synergistically enhances T-cell cytotoxicity by both activating epitope-specific T-cells and removing inhibitory checkpoints, achieving high productivity while managing protocol complexity through a coordinated dual-approach regimen

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS12551546B2Materials and methods relating to immunogenic epitopes from human papilloma virus

Publication Date: 2026.02.17 MT SINAI SCHOOL OF MEDICINE

AI summary

Embodiments of the present disclosure pertain generally to head and neck squamous cell carcinomas (HNSCCs) related to human papillomavirus subtype 16 (HPV16) infections. More particularly, the present disclosure provides novel immunogenic epitopes from HPV16 E2, E6 and E7 antigens restricted by common human leukocyte antigen (HLA) alleles for the diagnosis and treatment of HNSCC. The HPV16 epitopes identified in the present disclosure can be used in combination with blockade of HPV16+ HNSCC-specific checkpoints for targeted immunotherapy.