Retroviral Vector for Tumor Immune Modulation
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Solution Overview
Problem
Current cancer therapies face challenges in effectively treating solid tumors and micrometastases due to toxicity issues with chemotherapeutic agents and limited success in modulating the immune response, particularly in inhibiting immune suppressive molecules expressed by tumors.
Innovation Solution
A recombinant retroviral vector is developed that comprises multiple expression cassettes, including those encoding inhibitory nucleic acid sequences and polypeptides such as cytosine deaminase, to downregulate immune inhibitory agents like PD-L1 and IDO1, using promoters like CMV and mini-promoters for efficient transcription in mammalian cells, allowing for targeted delivery of anti-tumor agents directly to tumors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemotherapeutic agents are used to treat solid tumors and micrometastases, then tumor growth can be inhibited, but toxicity to normal tissues occurs
Solution Approach 1:
The patent applies local quality by using retroviral vectors to deliver immune-modulating genes specifically to tumor cells and tumor microenvironment. The vector system targets tumor cells through receptor-mediated entry, ensuring that immune-stimulating agents are produced locally at the tumor site rather than systemically, thereby treating tumors while sparing normal tissues from toxicity
Solution Approach 2:
The patent uses retroviral vectors as intermediaries to deliver genetic material encoding immune-modulating proteins (such as cytokines, checkpoint inhibitors) into tumor cells. These vectors act as mediators that convert non-toxic genetic information into therapeutic proteins locally, avoiding the direct toxicity of chemotherapeutic agents while maintaining treatment efficacy
2Reliability
If immune suppressive molecules expressed by tumors are not targeted, then the immune response remains limited, but therapeutic strategies lack effectiveness
Solution Approach 1:
The patent converts the harmful immune-suppressing function of tumor-expressed molecules into a benefit by using retroviral vectors to deliver genes that encode immune-stimulating proteins. These vectors transform the tumor microenvironment from immunosuppressive to immunostimulatory, turning the tumor's ability to modulate immunity against the host into a therapeutic advantage
Solution Approach 2:
The patent changes the immunological parameters of the tumor microenvironment by introducing foreign genes that encode cytokines, checkpoint blockers, or other immune-modulating proteins. This alters the local immune landscape from suppressive to activating, enhancing T-cell infiltration and cytotoxic activity against tumor cells
3Reliability
If multiple expression cassettes are included in the vector to downregulate multiple immune inhibitory agents, then the immune response against tumors is enhanced, but the device complexity increases
Solution Approach 1:
The patent merges multiple therapeutic functions into a single retroviral vector by incorporating multiple expression cassettes that encode different immune-modulating proteins. This combined approach allows simultaneous delivery of multiple therapeutic agents (e.g., cytokines, checkpoint inhibitors) from one vector, enhancing immune response while avoiding the need for multiple separate treatments
Solution Approach 2:
The retroviral vector is designed as a multi-functional platform capable of delivering various types of genetic material (coding sequences, regulatory elements) to achieve multiple therapeutic effects. The vector system can be configured to express different combinations of immune-modulating proteins depending on the specific tumor type and clinical need, providing universal applicability across different cancer indications
Data Source
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AI summary
The disclosure provides vectors for treating cancers, method of producing such vectors and methods of use of the vectors.