EBV Antigen Conjugates for Fc-Independent Target Cell Elimination
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Solution Overview
Problem
Existing immunotherapies face limitations due to differential responses to therapeutic monoclonal antibodies (mAbs) correlated with Fc receptor gene sequences, and engineered Fc chain modifications can compromise target accessibility, necessitating alternative immunogenic agents that can induce effective immune responses without Fc effector functions.
Innovation Solution
Development of an immunogenic conjugate comprising an Epstein-Barr Virus (EBV) B-cell antigen, particularly from the P18 and P23 antigens, conjugated to a target-binding moiety such as antibodies or non-proteic molecules, which triggers opsonic phagocytosis, ADCC, and antibody-dependent complement activation without an Fc region.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If therapeutic monoclonal antibodies are used to eliminate target cells, then the elimination effectiveness is improved, but differential responses occur due to Fc receptor gene polymorphisms
Solution Approach 1:
The patent extracts the Fc region from the antibody structure, using only the antigen-binding variable regions (VHH, Fab, or scFv) to eliminate the target cell. This removes the source of Fc receptor polymorphism variability while preserving the antigen-specific binding capability, thereby ensuring consistent responses across different patients.
Solution Approach 2:
The patent introduces an Epstein-Barr Virus (EBV) B-cell antigen as an intermediary component conjugated to the antibody fragment. This EBV antigen acts as a mediator that bridges the antibody to the target cell, enabling immune response activation through alternative pathways that do not depend on Fc receptor polymorphisms.
2Reliability
If Fc chain is engineered in single chain antibodies to obtain Fc effector function, then the effector function capability is improved, but the accessibility to cryptic epitopes decreases
Solution Approach 1:
The patent extracts and uses only the essential antigen-binding variable regions of antibodies (VHH, Fab, or scFv) without incorporating the Fc region. This extraction approach achieves the desired effector function through alternative mechanisms while maintaining the compact size necessary for accessing cryptic epitopes in small cellular cavities and clefts.
Solution Approach 2:
The patent employs the patient's own pre-existing immune response to EBV antigens as a self-service mechanism. By conjugating the EBV B-cell antigen to the antibody fragment, the system leverages the patient's existing antibodies against EBV to mediate the immune response, eliminating the need for engineered Fc effector functions.
3Length of moving object
If VHH, Fab or scFv is used as targeting agent, then the accessibility to cryptic epitopes is improved, but the Fc effector function capability is lost
Solution Approach 1:
The patent merges two functional components: the antigen-binding antibody fragment (VHH, Fab, or scFv) and the EBV B-cell antigen. This combination creates a conjugate that retains the small size and epitope accessibility of the antibody fragment while gaining effector function capability through the EBV antigen component, which activates the patient's pre-existing immune response.
Data Source
Figure 1A~1B
Figure 1C~1D
Figure 2
AI summary
The present invention generally relates to an immunogenic construct,useful for redirecting an EBV-existing immune response towards an undesired target cell and/or microorganism,to methods for preparing said conjugate, to a pharmaceutical applications comprising said conjugate, and to medical applications thereof.