Co-expressing Targeted Polypeptides and Immunoinhibitory Compounds
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Solution Overview
Problem
Current immunosuppressive drugs for autoimmune diseases, allergic reactions, and graft rejection are broad-acting, leading to severe side effects such as immunodeficiency and increased susceptibility to infections, as they non-selectively suppress the immune system.
Innovation Solution
Development of vectors, such as DNA plasmids, that co-express a targeting unit and immunoinhibitory compounds to specifically deliver antigens to antigen-presenting cells, inducing antigen-specific tolerance without activating an inflammatory immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If broad-acting immunosuppressive drugs are used to prevent or reduce undesirable immune responses, then immune tolerance is achieved, but severe side effects occur including immunodeficiency and increased susceptibility to infections
Solution Approach 1:
The invention segments the immune system suppression function by using antigen-specific tolerogenic APCs to target only pathogenic immune responses against specific antigens (such as self-antigens in autoimmune diseases or donor antigens in graft rejection), rather than using broad-acting drugs that suppress the entire immune system. This segmentation allows selective immunosuppression of disease-causing immune responses while preserving protective immune functions.
Solution Approach 2:
The invention applies local quality by creating a tolerogenic microenvironment at the site of antigen presentation through modified APCs that express specific tolerogenic signals (such as altered MHC expression, co-stimulatory molecules, or cytokine profiles). This localized tolerogenic effect is delivered precisely where immune responses are initiated, affecting only antigen-specific T cells while leaving other immune functions intact.
2Reliability
If conventional immunosuppressive drug therapy is used to maintain immunosuppression, then undesirable immune responses are controlled, but the immune system becomes non-selectively suppressed leading to increased susceptibility to infections and decreased cancer immunosurveillance
Solution Approach 1:
The invention divides immune suppression into antigen-specific segments by engineering APCs to present specific antigens in a tolerogenic manner. This allows precise control over which immune responses are suppressed (only those against the specific antigen) while preserving other immune functions, achieving high selectivity that conventional broad-acting drugs cannot provide.
Solution Approach 2:
The invention introduces tolerogenic APCs as intermediary cells that mediate antigen-specific tolerance induction. These engineered APCs act as selective intermediaries between the antigen and the immune system, delivering tolerogenic signals only to T cells specific for the target antigen, thereby achieving precise control without broad immunosuppression.
3Reliability
If antigen is delivered to APCs using conventional methods, then immune response regulation is attempted, but inflammatory immune response is triggered instead of tolerance induction
Solution Approach 1:
The invention changes key parameters of the APC state to induce tolerance rather than inflammation. This includes modifying APC activation status, cytokine production profiles, surface molecule expression (such as co-stimulatory molecules like CD80/CD86, or checkpoint molecules like PD-L1), and metabolic state. These parameter changes create a tolerogenic microenvironment that promotes T cell anergy or regulatory T cell differentiation instead of inflammatory activation.
Solution Approach 2:
The invention converts the potentially harmful inflammatory response into a beneficial tolerogenic response by engineering APCs to deliver controlled tolerogenic signals. The APCs are modified to express specific molecules or cytokines that actively promote tolerance (such as IL-10, TGF-β, or altered MHC class II expression), transforming the antigen presentation process from potentially inflammatory to consistently tolerogenic.
Data Source
AI summary
The present invention relates to vectors, such as DNA plasmids, comprising multiple nucleic acid sequences engineered to be co-expressed as separate molecules. Such separate molecules include a first polypeptide, wherein the first polypeptide comprises a targeting unit that targets antigen-presenting cells, a multimerization unit, such as dimerization unit, and an antigenic unit comprising one or more T cell epitopes of a self-antigen, an allergen, an alloantigen or a xenoantigen, and one or more immunoinhibitory compounds