Local Dendritic Cell and Checkpoint Inhibitor Administration for Tumour Treatment
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Solution Overview
Problem
Current cancer immunotherapy methods face challenges in effectively targeting tumour-specific antigens and managing immune responses, particularly in prostate cancer where tumour heterogeneity and the presence of regulatory T cells can limit treatment efficacy and increase adverse side effects.
Innovation Solution
The method involves administering autologous immature dendritic cells and an immune cell checkpoint inhibitor locally to the site of a partially ablated tumour, leveraging tumour neoantigens and promoting an anti-tumour immune response while minimizing systemic side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune cell checkpoint inhibitors are administered systemically to stimulate anti-tumour immune response, then treatment efficacy against tumour cells is improved, but adverse side effects increase
Solution Approach 1:
The patent applies local quality by administering immune cell checkpoint inhibitors directly to the ablated tumour site rather than systemically. This localized administration concentrates the therapeutic effect at the tumour location while reducing exposure to healthy tissues, thereby maintaining treatment efficacy against tumour cells while minimizing adverse side effects such as autoimmune reactions and inflammatory responses in normal organs.
Solution Approach 2:
The treatment protocol segments the immunotherapy process into distinct phases: first ablating the tumour to release neoantigens, then administering dendritic cells to present these antigens, and finally applying immune cell checkpoint inhibitors locally to enhance the immune response. This segmentation allows each component to function optimally at the appropriate stage, improving overall efficacy while controlling side effects through targeted delivery.
2Quantity of substance
If tumour ablation is performed to release tumour antigens, then antigen availability for immune response is improved, but surrounding tissue damage increases
Solution Approach 1:
The patent introduces dendritic cells as an intermediary between tumour ablation and immune response. After ablation releases tumour antigens, dendritic cells are administered to selectively uptake and present these antigens to T cells. This intermediary step concentrates the immune activation at the tumour site while protecting surrounding healthy tissues from direct damage by the ablation process and excessive immune activation.
Solution Approach 2:
The patent converts the harmful effect of tumour ablation (potential tissue damage and inflammation) into a beneficial outcome by using the ablated tumour material as a source of neoantigens. The ablation process, while potentially damaging, successfully releases tumour-associated antigens that are then presented by dendritic cells to generate a specific anti-tumour immune response, transforming the harmful ablation side effects into useful antigen exposure.
3Measurement precision
If dendritic cells are administered to present tumour antigens, then immune response specificity is improved, but treatment complexity increases
Solution Approach 1:
The patent employs autologous dendritic cells that are harvested from the patient's own body and administered back to present patient-specific tumour antigens. This self-service approach ensures high immune response specificity tailored to each patient's unique tumour neoantigens while avoiding the complexity of generating allogeneic cell lines or synthetic antigen formulations. The patient's own cells perform the antigen presentation function, simplifying the overall treatment protocol.
Data Source
Figure 1A~1B
AI summary
The present invention provides a method for the treatment of a tumour in a subject, said method comprising administering (i) an autologous immature dendritic cell, or a precursor thereof, and (ii) an immune cell checkpoint inhibitor to said subject subsequent to the at least partial ablation of said tumour in said subject, wherein the administration of said autologous immature dendritic cells, or a precursor thereof, and said immune cell checkpoint inhibitor is local to the site of the ablated tumour or part thereof. The invention further provides a product containing an autologous immature dendritic cell, or a precursor thereof, and an immune cell checkpoint inhibitor as a combined preparation for separate, simultaneous or sequential use in a method for the treatment of a tumour in a subject, said method comprising administering (i) the autologous immature dendritic cell, or a precursor thereof, and (ii) the immune cell checkpoint inhibitor to said subject subsequent to the at least partial ablation of said tumour in said subject, wherein the administration of said autologous immature dendritic cells, or a precursor thereof, and said immune cell checkpoint inhibitor is local to the site of the ablated tumour or part thereof.