Immunomodulatory Polypeptides Targeting Tumor Cells
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Solution Overview
Problem
Current treatments for diseases such as cancer using cytokines or chemokines often result in adverse effects and reduced efficacy due to systemic administration and immunogenicity.
Innovation Solution
Development of immunomodulatory polypeptides comprising a first and second peptide connected by a joining region with a targeting moiety that binds to a specific target molecule, enhancing targeted delivery and reducing systemic toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cytokines or chemokines are administered systemically for cancer treatment, then therapeutic activity is achieved, but adverse effects and systemic toxicity increase
Solution Approach 1:
The patent applies local quality by designing immunomodulatory polypeptides with targeting moieties that direct the therapeutic agent to specific tumor cells or tissues. The polypeptide structure includes a cytokine or chemokine portion coupled to a targeting moiety that recognizes specific markers on tumor cells, ensuring the therapeutic effect is localized to the disease site rather than distributed systemically. This resolves the contradiction by maintaining therapeutic activity at the target site while minimizing adverse effects in healthy tissues.
Solution Approach 2:
The patent uses the targeting moiety as an intermediary that mediates between the immunomodulatory polypeptide and the target cell. The targeting moiety (such as an antibody fragment or ligand) specifically binds to receptors or markers on tumor cells, facilitating selective delivery of the cytokine or chemokine portion. This intermediary mechanism enables precise targeting, achieving therapeutic effects while reducing systemic toxicity and adverse reactions.
2Productivity
If cytokines or chemokines are administered to enhance immune response, then efficacy increases, but immunogenicity and adverse reactions worsen
Solution Approach 1:
The patent reduces immunogenicity by localizing the immunomodulatory effect to the tumor microenvironment through targeted delivery. The cytokine or chemokine portion is delivered specifically to tumor sites via the targeting moiety, avoiding widespread exposure that would trigger systemic immune responses. This localized approach maintains high efficacy at the target site while minimizing immunogenicity and adverse reactions in healthy tissues.
Solution Approach 2:
The patent converts the potential harm of immunogenicity into a benefit by using the targeting moiety to direct the immunomodulatory effect precisely where needed. The specific binding of the targeting moiety to tumor cell markers ensures that the immunogenic cytokine or chemokine portion is delivered only to the desired site, transforming what could be a harmful systemic immune response into a beneficial localized anti-tumor immune response.
3Measurement precision
If targeting moiety is added to achieve specific binding, then binding specificity increases, but molecular complexity and manufacturing difficulty worsen
Solution Approach 1:
The patent creates a composite molecular structure by coupling a cytokine or chemokine portion to a targeting moiety. This composite immunomodulatory polypeptide combines the therapeutic activity of the cytokine/chemokine with the specific binding capability of the targeting moiety (such as an antibody fragment or ligand). The composite structure achieves high binding specificity for tumor cells while the modular design facilitates standardized manufacturing processes and quality control.
Data Source
AI summary
Provided herein are immunomodulatory polypeptides containing first and second submits of a cytokine or a chemokine connected by a joining region containing a targeting moiety that binds to a target molecule. In some aspects, the disclosure further relates to engineered cells and compositions comprising the immunomodulatory polypeptides and methods for their administration to subjects. In some embodiments, the cells engineered to contain the immunomodulatory polypeptide, such as T cells, further contain a genetically engineered antigen receptor that specifically binds to antigens, such as a chimeric antigen receptor (CAR). In some embodiments, features of the polypeptides, engineered cells, and methods provide for improved treatment of diseases or disorders, such as by reducing adverse effects of cytokine or chemokine therapy, or increasing activity, efficacy and/or persistence or decreasing immunogenicity of adoptive cell therapy.