Cellular Adjuvants for Viral Uptake in Receptor-Deficient Immune Cells
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Solution Overview
Problem
Existing immunotherapies using recombinant viral particles face challenges in achieving effective immune responses due to the lack of viral uptake and expression in immune competent cells, particularly those lacking receptors like CXADR, and conventional adjuvants may not be beneficial or can skew immune responses.
Innovation Solution
The use of cell-based adjuvants, such as non-host cells like bacteria (e.g., ΔLPS-E. coli) or yeast cells (e.g., S. cerevisiae), which stimulate immune responses and enhance viral uptake and expression of recombinant antigens in immune competent cells, even in the absence of specific receptors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional adjuvants are used to stimulate immune response, then immune reaction is potentiated, but immune response may be skewed or not beneficial for recombinant viral particles
Solution Approach 1:
The patent uses CXADR-expressing cells as intermediary carriers that facilitate the delivery of recombinant viral particles to immune competent cells. These intermediary cells overcome the limitation that immune competent cells lack CXADR receptors, thereby enabling effective delivery without requiring modification of the viral particles themselves or using conventional adjuvants that may skew immune responses.
Solution Approach 2:
The patent replaces the conventional adjuvant-based immune stimulation mechanism with a receptor-mediated cellular uptake mechanism. Instead of using chemical adjuvants to potentiate immune response, the invention uses the CXADR-XCR1 receptor-ligand interaction to enable specific cellular uptake and delivery of viral particles, substituting a biological recognition system for a chemical stimulation system.
2Reliability
If recombinant viral particles are used for immunotherapy, then antigen production within cells is triggered, but viral uptake by immune competent cells is insufficient due to lack of receptors
Solution Approach 1:
CXADR-expressing cells serve as intermediary vehicles that solve the dual problem of enabling viral particle delivery to immune competent cells while maintaining antigen production. These intermediary cells express the CXADR receptor that binds viral particles, internalize them, and then present the antigens to immune cells, thereby bridging the gap between viral delivery and immune stimulation without requiring direct viral uptake by immune competent cells.
Solution Approach 2:
The patent segments the immunotherapy process into two distinct functional components: (1) CXADR-expressing cells that handle viral particle uptake and antigen production, and (2) immune competent cells that receive antigen presentation and mount immune responses. This segmentation allows each cell type to perform its optimal function without the limitation of requiring both viral uptake capability and immune competence in a single cell type.
3Object-affected harmful factors
If viral particles are designed to be non-immunogenic to avoid immune reaction against the vector, then therapeutic safety is improved, but immune competent cells cannot uptake the virus effectively
Solution Approach 1:
The CXADR-expressing cell acts as an intermediary that decouples the requirements for viral uptake and immune stimulation. The viral particles can remain non-immunogenic and still be effectively taken up by CXADR-expressing cells, which then process and present antigens to immune competent cells. This intermediary system enables effective delivery without requiring the viral particles to be immunogenic themselves.
Data Source
AI summary
Two-component vaccine formulations and methods are contemplated where the vaccine has an adjuvant component and a therapeutic component. The therapeutic component comprises preferably a recombinant therapeutic virus encoding a therapeutic antigen while the adjuvant component comprises a non-host cell or immune stimulating portion thereof. Notably, use of the adjuvant component will result in significant uptake of the therapeutic component into immune competent cells, even in the absence of receptors for entry of the therapeutic component. In addition, such adjuvant also stimulates expression of the therapeutic antigen.