Hypoimmunogenic Cells Evading Immune Detection
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Solution Overview
Problem
Clinical transplantation therapies face challenges due to immune system rejection of allogeneic material, which reduces the efficacy of treatments and limits the positive effects of therapies.
Innovation Solution
Administration of hypoimmunogenic cells modified to express reduced levels of MHC class I and II antigens, beta-2-microglobulin, and MHC class II transactivator, encoded by exogenous polynucleotides, to evade immune detection, particularly in sensitized patients undergoing or having undergone transplants, pregnancies, or previous treatments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If allogeneic cells are administered to treat a patient, then therapeutic effect is achieved, but immune rejection occurs reducing treatment efficacy
Solution Approach 1:
The patent applies this principle by modifying cells to express hypoimmunogenic characteristics - specifically reducing MHC class I and class II expression and increasing CD47 expression. These modifications convert the cells' normal immunogenic properties into hypoimmunogenic properties, allowing them to evade immune detection and rejection while maintaining therapeutic function. The harmful immune rejection response is transformed into a beneficial state where the immune system tolerates the allogeneic cells.
Solution Approach 2:
The patent implements parameter changes by altering key immunological parameters of the cells: downregulating MHC class I and class II molecules, modifying beta-2-microglobulin expression, and adjusting CD47 surface levels. These parameter modifications fundamentally change the cells' interaction with the immune system, enabling them to withstand immune pressure and achieve long-term engraftment and therapeutic effect in sensitized patients.
2Object-affected harmful factors
If cells with reduced MHC expression are used to evade immune detection, then immune rejection is reduced, but immune evasion capability must be enhanced
Solution Approach 1:
The patent applies this principle by creating composite cellular structures that combine multiple modified components: cells with reduced MHC class I and class II expression, modified beta-2-microglobulin levels, and enhanced CD47 expression. This composite approach integrates multiple immunomodulatory modifications into a single cell type, achieving synergistic immune evasion effects while managing the complexity through a unified modification strategy.
3Object-affected harmful factors
If hypoimmunogenic cell modifications are implemented, then immune detection is avoided, but manufacturing complexity increases
Solution Approach 1:
The patent implements preliminary action by performing all necessary immunomodulatory modifications during the cell manufacturing and expansion phase, before administration to the patient. The cells are pre-modified to express the hypoimmunogenic phenotype (reduced MHC, enhanced CD47) through genetic or epigenetic modifications established during culture expansion. This preliminary modification ensures that when the cells are administered, they already possess the required immune evasion characteristics without requiring additional complex steps at the time of treatment.
Data Source
AI summary
Disclosed herein are hypoimmunogenic cells for administering to a sensitized patient. In some instances, the patient is sensitized from a previous pregnancy or a previous transplant. In some embodiments, the cells exogenously express CD47 proteins and exhibit reduced expression of MHC class I proteins, MHC class II proteins, or both.