Protein-Steroid Conjugates for Targeted Glucocorticoid Delivery
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Solution Overview
Problem
Existing glucocorticoid treatments suffer from toxicities due to ubiquitous expression of glucocorticoid receptors in various cell types, leading to side effects in non-target cells.
Innovation Solution
Development of antibody-drug conjugates comprising glucocorticoid payloads, specifically protein-steroid conjugates that target glucocorticoid receptors with high specificity, minimizing side effects by delivering glucocorticoids only to target cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If glucocorticoid treatments are administered to treat inflammatory conditions, then anti-inflammatory efficacy is improved, but toxicities and side effects increase due to ubiquitous glucocorticoid receptor expression in non-target cells
Solution Approach 1:
The invention segments the glucocorticoid treatment by separating the targeting function (antibody) from the therapeutic function (glucocorticoid payload). The antibody component directs the treatment to specific target cells expressing the target antigen, while the glucocorticoid payload delivers the anti-inflammatory effect. This segmentation allows the treatment to affect only target cells rather than all cells expressing glucocorticoid receptors, thereby maintaining efficacy while reducing off-target toxicities.
Solution Approach 2:
The antibody-drug conjugate serves as an intermediary that bridges the specificity of antibodies and the potency of glucocorticoids. The antibody portion acts as a delivery vehicle that specifically binds to target cells, and the glucocorticoid payload is released at the target site to exert its anti-inflammatory effect. This intermediary approach enables precise delivery of glucocorticoids to target cells while minimizing exposure and toxicities in non-target cells.
2Adaptability or versatility
If conventional glucocorticoids are used, then broad anti-inflammatory coverage is achieved, but specificity to target cells is lost leading to systemic side effects
Solution Approach 1:
The invention applies local quality by making the glucocorticoid treatment cell-type-specific through the antibody component. Different antibody-drug conjugates can be designed with different antibody specificities to target different cell types expressing different antigens. This allows the treatment to have broad adaptability across various inflammatory conditions while maintaining high specificity to the intended target cells, as each conjugate is tailored to its specific target.
Data Source
AI summary
Described herein are protein steroid conjugates that are useful, for example, for the target-specific delivery of glucocorticoids (GCs) to cells.