Antigen-Presenting Cell MHC Tumor Antigen Co-Expression

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Solution Overview

Problem

Current anticancer therapeutic cell vaccines face limitations due to MHC restriction, which restricts the range of antigen-presenting epitope sequences and overall antigen presentation efficacy, as they rely on specific MHC alleles already expressed in cells.

Innovation Solution

A vaccine composition comprising antigen-presenting cells with a complex of major histocompatibility complex (MHC) and tumor antigens overexpressed on their surface, achieved by introducing a bicistronic gene construct or mRNA transcript co-expressing patient-specific MHC and tumor antigens, maximizing epitope-MHC immunostimulatory complex expression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If epitope peptide incubation method is used for antigen loading, then antigen presentation can be achieved, but the range of antigen-presenting epitope sequences is restricted and overall antigen presentation efficacy is limited due to MHC restriction

Engineering Contradiction:

Improverange of antigen-presenting epitope sequencesVSAvoidantigen presentation efficacy

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent changes the fundamental parameter of antigen loading from external peptide incubation to endogenous expression through bicistronic mRNA transfection. This allows the antigen-presenting cells to express patient-specific MHC alleles and tumor antigens simultaneously, overcoming the MHC restriction limitation while maintaining high antigen presentation efficacy through maximal complex expression on the cell surface

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces bicistronic mRNA as an intermediary that enables simultaneous expression of MHC alleles and tumor antigens within the same antigen-presenting cell. This mRNA intermediary bypasses the need for separate peptide loading and MHC expression steps, allowing direct co-expression and assembly of complete epitope-MHC complexes

Inventive Principle:

Principle #24Intermediary (Mediator)

2Ease of manufacture

If standardized antigen-presenting cells are used, then manufacturing consistency is improved, but MHC restriction of individual antigen-presenting cells limits the applicability to patient-specific neoantigens

Engineering Contradiction:

Improvestandardization of cell vaccine productionVSAvoidpatient-specific neoantigen applicability

Core Design Contradiction:

Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent creates a dynamic system where standardized antigen-presenting cells can be flexibly programmed with patient-specific bicistronic mRNA constructs. The cells maintain their standardized manufacturing advantages while dynamically adapting to express any patient-specific MHC allele and tumor antigen combination through transfection with customized mRNA, enabling both standardization and personalization

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent makes standardized antigen-presenting cells universal by enabling them to express multiple different patient-specific MHC alleles and tumor antigens through bicistronic mRNA transfection. The same cell platform can be adapted to any patient's neoantigens, making the manufacturing system universally applicable across different patients while maintaining production consistency

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20230338530A1Composition comprising antigen-presenting cell co-expressing MHC and tumor antigen, and cancer treatment using same

Publication Date: 2023.10.26 LG CHEM LTD

AI summary

Provided are a vaccine composition for preventing or treating cancer, the vaccine composition comprising antigen-presenting cells, on the cell surface of which a complex of a major histocompatibility complex (MHC) and a tumor antigen is overexpressed, and cancer treatment using the same.