Dendritic Cell Dual Antigen Loading for Immune Activation
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Solution Overview
Problem
Current immune therapy strategies using dendritic cells for cancer treatment face challenges in achieving a sustained adaptive immune response and are limited by the inefficiency of DC maturation and antigen loading methods, which fail to induce a robust and long-lasting immune response against tumors.
Innovation Solution
Dendritic cells are loaded with both nucleic acid molecules encoding tumor-associated antigens, such as TERT, and protein antigens like Survivin, to trigger both cytotoxic and adaptive immune responses, enhancing their maturation and functionality, including reduced phagocytic capability, increased IL-12 secretion, and surface antigen expression, allowing for targeted immune activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dendritic cells are loaded with both nucleic acid molecules and protein antigens, then the immune response is significantly enhanced, but the device complexity and manufacturing difficulty increase
Solution Approach 1:
The patent applies preliminary action by pre-loading dendritic cells with nucleic acid molecules encoding tumor antigens before maturation, so that the cells are already primed to produce the antigen proteins endogenously. This preliminary loading ensures that when the cells mature and encounter T cells, they can immediately present both the synthesized antigen (from nucleic acid expression) and any co-loaded protein antigens, thereby enhancing the immune response without requiring complex post-maturation manipulation.
Solution Approach 2:
The patent uses nucleic acid molecules (mRNA or DNA) as an intermediary that serves dual functions: they encode tumor-associated antigens that will be expressed by the dendritic cells, and they can be co-administered with protein antigens. This intermediary approach allows the dendritic cells to become factories producing the antigen, thereby amplifying the immune stimulus without requiring direct complex manipulation of the antigen-protein mixture, simplifying the overall process while maintaining effectiveness.
2Manufacturing precision
If dendritic cells are matured in vitro with standard cocktails, then they express maturation markers, but they fail to induce a robust and long-lasting immune response against tumors
Solution Approach 1:
The patent applies parameter changes by modifying the maturation conditions of dendritic cells through specific cytokine combinations (such as IL-1β, IL-6, TNF-α, and PGE2) and controlling the timing and sequence of antigen loading relative to maturation induction. By optimizing these parameters—cytokine concentrations, incubation times, and the order of operations—the patent achieves both proper maturation marker expression and enhanced capacity to induce sustained immune responses against tumors.
Solution Approach 2:
The patent uses preliminary action by loading dendritic cells with antigen-coding nucleic acid molecules before inducing maturation. This ensures that the cells begin producing the antigen early in the maturation process, allowing for sustained antigen presentation over time. The antigen is produced endogenously by the maturing DCs themselves, which prolongs the duration of antigen availability to T cells compared to simple protein loading that would be gradually degraded.
3Reliability
If dendritic cells are used for cancer immunotherapy, then they can activate the immune system against tumors, but their function is impaired by high levels of IL-10 secretion which creates a tolerogenic state
Solution Approach 1:
The patent converts the harmful effect of IL-10-mediated immunosuppression into a benefit by utilizing the natural IL-10 secreting capability of dendritic cells in a controlled manner. Rather than attempting to completely block IL-10 production, the patent optimizes the maturation conditions and antigen loading strategies to ensure that IL-12 and other pro-inflammatory cytokines are produced in sufficient quantities to override the tolerogenic effects of IL-10. This approach acknowledges the presence of IL-10 but designs the system to succeed despite it, turning a potential weakness into an acceptable parameter of the immunotherapy protocol.
Data Source
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AI summary
The present invention relates to dendritic cell loaded with at least one nucleic acid molecule encoding a tumor associated antigen protein or fragment thereof and at least one tumor associated antigen protein or fragment thereof.