Radiation-Linked Target Screening for Tumor Immune Suppression
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Solution Overview
Problem
The tumor microenvironment is inherently inhibitory due to the presence of myeloid-derived suppressor cells and regulatory T cells, limiting effective immune responses against cancer, and radiation therapy modulates this environment but requires methods to identify target factors for therapeutic intervention.
Innovation Solution
In vitro and in vivo screening methods using T cell suppression assays in combination with radiation treatment to identify target genes that modulate the tumor microenvironment, involving T cells with candidate genes knocked-down or knocked-out to assess activity changes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If radiation therapy is used to treat cancer, then anti-tumor effects are achieved through induction of apoptosis and senescence, but the tumor microenvironment remains inhibitory due to suppressor cells and regulatory T cells
Solution Approach 1:
The patent segments the complex tumor microenvironment problem into specific targetable factors (CXCL12, CCL5, PD-L1, etc.) that can be individually addressed. By identifying and isolating specific molecules and cells responsible for suppression, the therapy can target these discrete elements rather than treating the entire microenvironment as a single entity.
Solution Approach 2:
The patent introduces intermediary molecules and cells as therapeutic agents that mediate between the radiation therapy and the tumor microenvironment. These intermediaries (such as antibodies against CXCL12, CCL5, or PD-L1) act as bridges to block suppressive interactions and enhance anti-tumor immunity without directly confronting the entire microenvironment.
2Adaptability or versatility
If suppressor cells and regulatory T cells are present in the tumor microenvironment, then immune responses are suppressed, but identifying specific target factors requires complex screening methods
Solution Approach 1:
The screening methodology is segmented into distinct, manageable components: in silico prediction of radiation-responsive genes, in vitro functional assays with T cells and suppressor cells, and in vivo validation in tumor models. This segmentation allows each component to be optimized independently and simplifies the overall complex screening process.
Solution Approach 2:
The patent employs dynamic screening approaches that adapt to different experimental conditions and cell types. The methodology can dynamically adjust parameters such as radiation dosage, cell ratios, and assay timepoints to optimize detection of target factors across diverse tumor microenvironment contexts.
Data Source
AI summary
In vitro and in vivo methods for screening for targets for cancer therapy are provided herein. Methods contemplate screening for targets that contribute to the immunosuppressive environment for the tumor cells, especially those targets that are associated with radiation treatment. Thus, methods provided herein are useful for identifying potential targets useful for providing cancer therapeutic agents that can be used either alone or in combination with radiation therapy.