Immune Cell Modulation for Adoptive Immunotherapy Efficacy
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Solution Overview
Problem
Current adoptive immunotherapies face challenges in enhancing the therapeutic efficacy of immune cells, such as CAR-T cells, NK cells, and NKT cells, due to limitations in potency, persistence, migration, and safety issues, as well as the complexity of tumor microenvironments and heterogeneity, which affect the quality and quantity of therapeutic cells.
Innovation Solution
The use of specific modulating agents, including Dorsomorphin, Heptelidic acid, and other compounds listed in Table 1, to improve the proliferation, persistence, cytotoxicity, and differentiation of immune cells, thereby enhancing their therapeutic potential by modulating cell metabolism, signal transduction, and apoptosis pathways.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If immune cells are expanded ex vivo for adoptive therapy, then the quantity of therapeutic cells is improved, but the differentiation state changes leading to reduced persistence and potency
Solution Approach 1:
The patent applies preliminary action by treating immune cells with modulating agents (such as dorsomorphin, heptelidic acid, or other compounds) during the ex vivo expansion process before transplantation. This pre-treatment maintains the desired differentiation state (naïve or central memory phenotype) during expansion, ensuring that the expanded cell population retains persistence and potency capabilities while achieving the required quantity for therapy.
2Reliability
If immune cells are activated and differentiated to enhance cytotoxicity, then the therapeutic potency is improved, but the persistence and memory formation are reduced
Solution Approach 1:
The patent employs parameter changes by using small molecule modulating agents that specifically alter the differentiation parameters of immune cells during expansion. These agents (e.g., dorsomorphin, heptelidic acid, or compounds from Table 1) modulate signaling pathways to maintain naïve or central memory phenotypes while still enabling functional activation, thereby achieving both high potency and long-term persistence in the therapeutic cell product.
3Reliability
If the tumor microenvironment is complex and immunosuppressive, then the safety and efficacy are improved, but the migration and infiltration of therapeutic cells are hindered
Solution Approach 1:
The patent applies preliminary action by pre-modulating immune cells with specific agents that enhance their migratory capabilities and equip them to counteract the immunosuppressive tumor microenvironment before transplantation. This preparation includes upregulating chemokine receptors and adhesion molecules, enabling the cells to efficiently home to and infiltrate tumor sites while maintaining safety and efficacy profiles.
Data Source
AI summary
Compounds that either produced a higher proportion or greater absolute number of phenotypically identified naive, stem cell memory, central memory T cells, adaptive NK cells, and type I NKT cells are identified. Compositions and methods for modulating immune cells including T, NK, and NKT cells for adoptive cell therapies with improved efficacy are provided.