Tumor Characterization Using Nanoparticle Cytokine Profiling
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Solution Overview
Problem
Current cancer immunotherapy methods, such as immune checkpoint inhibitors, are ineffective for immunologically 'cold' tumors, lacking an adaptive immune response, and there is a need for a method to identify tumors responsive to immunotherapy.
Innovation Solution
A method involving culturing tumor cells with nanoparticles comprising a positively-charged surface and an interior with at least two nucleic acid layers between cationic lipid bilayers, measuring interferon-alpha, CXCL10, and interleukin-6 production to characterize tumor responsiveness to immunotherapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint inhibitors are used for cancer immunotherapy, then treatment effectiveness is improved for immunologically active tumors, but treatment failure occurs for immunologically inactive tumors
Solution Approach 1:
The patent applies preliminary action by measuring interferon-alpha, CXCL10, and IL-6 production levels in tumor cells before administering immunotherapy. This pre-treatment characterization identifies tumors likely to respond to immunotherapy, allowing clinicians to select appropriate patients beforehand and avoid treatment failure in cold tumors.
Solution Approach 2:
The patent uses interferon-alpha, CXCL10, and IL-6 as intermediary biomarkers to mediate the assessment between tumor characteristics and immunotherapy response. These cytokines serve as measurable indicators that bridge the gap between tumor immunology and treatment effectiveness, enabling predictive characterization without direct measurement of treatment response.
2Measurement precision
If tumor cells are characterized by measuring cytokine production, then tumor responsiveness is identified, but the complexity of the characterization method increases
Solution Approach 1:
The patent applies segmentation by dividing the tumor characterization into separate measurable components: interferon-alpha, CXCL10, and IL-6 production levels. Each cytokine can be measured independently using standard assays, allowing the complex concept of tumor immunogenicity to be broken down into manageable, quantifiable parameters that can be assessed separately and combined for overall characterization.
Data Source
AI summary
The present disclosure provides a method of identifying a tumor for immunotherapy. The method comprises culturing tumor cells obtained from a subject; exposing the tumor cells to nanoparticles comprising a positively-charged surface and an interior comprising (i) a core and (ii) at least two nucleic acid layers, wherein each nucleic acid layer is positioned between a cationic lipid bilayer; and measuring interferon-alpha and interleukin 6 (and optionally Chemokine (C-C motif) ligands 4) produced by the tumor cells. A method of treating a subject with cancer also is provided. The method comprises culturing tumor cells from the subject; exposing the tumor cells to the nanoparticles; measuring interferon-alpha and interleukin 6 (and optionally Chemokine (C-C motif) ligands 4) produced by the tumor cells; and administering an immune checkpoint inhibitor to the subject. Any of the methods may also comprise measuring CXCL 10.