Conjugated VLP Tumor Targeting With Recall T Cell Redirection
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Solution Overview
Problem
Current cancer treatments, such as chemotherapy, radiation, and immunotherapies, are invasive, toxic, and ineffective against metastatic cancers due to immune tolerance and lack of broad applicability, with checkpoint inhibitors having a low responder rate and high development costs.
Innovation Solution
Conjugated virus-like particles (VLPs) that bind tumors, comprising a capsid protein and a fusion protein with a cleavage sequence and recall proteins, eliciting a T cell response through preexisting T cells to target cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If checkpoint inhibitor drugs are used to block immunosuppressive pathways, then the body's immune system is assisted in fighting cancer, but the treatment is ineffective in the majority of patients with a 70% non-responder rate
Solution Approach 1:
The patent introduces VLPs as intermediary carriers that deliver recall proteins to the tumor microenvironment. These VLPs act as mediators between the immune system and cancer cells, facilitating T cell recruitment and activation without relying on checkpoint pathways. The VLPs carry recall proteins that can be cleaved by tumor-associated proteases, releasing immunogenic peptides that activate pre-existing T cells locally at the tumor site.
Solution Approach 2:
The invention utilizes the tumor's own protease activity against it by designing recall proteins with cleavage sequences that are specifically recognized and cleaved by tumor-associated proteases. This self-service mechanism allows the tumor's enzymatic activity to inadvertently release immunogenic peptides that activate the immune system against the tumor, turning the tumor's biochemical environment into a therapeutic advantage.
2Object-affected harmful factors
If cancer vaccines based on cancer-associated antigens are used, then targeted elimination of cancer cells is achieved, but clinical immunogenicity is poor and immune tolerance occurs
Solution Approach 1:
Instead of using cancer-associated antigens that the immune system tolerates, the patent inverts the approach by using recall proteins from pathogens to which the patient has been previously exposed. These recall proteins elicit strong immune responses because they are recognized as foreign, not self. The VLPs deliver these non-self antigens to the tumor microenvironment, where they activate pre-existing pathogen-specific T cells to attack the tumor.
Solution Approach 2:
The patent changes the antigenic parameter from cancer-associated self-antigens to pathogen-derived recall antigens. This parameter change transforms the immune response from tolerant to activated, as the immune system recognizes pathogen-derived peptides as foreign threats rather than self-components. The cleavage sequence design further modulates the release kinetics and immunogenicity of the recall proteins.
3Reliability
If neoepitopes are used as antigens for cancer vaccines, then cancer-specific T cell responses are revived, but the therapy is highly personalized with lengthy development time and high costs
Solution Approach 1:
The patent employs universal recall proteins from common pathogens (such as influenza, measles, mumps, rubella, polio, hepatitis B, and varicella zoster) that have broad population coverage. These recall proteins can be used across different cancer types and patient populations without requiring personalized antigen identification. The VLP platform can accommodate multiple different recall proteins, providing a universal therapeutic approach that works across diverse patient groups.
Solution Approach 2:
The invention leverages pre-existing T cell immunity from prior pathogen exposures or vaccinations. By using recall proteins from pathogens to which the patient has already been exposed, the therapy activates pre-existing memory T cells rather than requiring de novo T cell priming. This preliminary action of prior immune exposure eliminates the need for lengthy antigen screening and personalized vaccine development.
4Reliability
If surgery is used to treat cancer, then invasive removal of tumors is achieved, but the treatment is highly invasive and often fails after metastasis
Solution Approach 1:
The patent replaces mechanical surgical removal with a biochemical-immunological approach. Instead of physically cutting and removing tumors, the therapy uses VLPs to deliver recall proteins that activate the immune system to selectively recognize and destroy cancer cells. This substitution of mechanical intervention with immunological mechanisms provides a less invasive alternative that can reach metastatic sites throughout the body.
Solution Approach 2:
The invention enables the patient's own immune system to perform the therapeutic function of tumor elimination. By activating pre-existing pathogen-specific T cells through recall protein delivery, the body's immune system becomes the active agent in destroying cancer cells, replacing the need for external mechanical intervention. This self-service approach allows the immune system to autonomously seek out and eliminate both primary and metastatic tumors.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The VLPs induce a strong, durable T cell response, inhibiting tumor growth and metastasis without immune tolerance, applicable to various cancers, and overcoming limitations of existing treatments.
Implementation Method 1
a capsid protein, wherein said capsid protein is capable of binding, or binds to, a cancer cell
Implementation Method 2
a fusion protein comprising at least a protein cleavage sequence, wherein the protein cleavage sequence is preferentially cleaved in the presence of a tumor
Implementation Method 3
at least one recall protein, wherein said recall protein is a protein or fragment thereof having a sequence that is an epitope capable of being bound by, or is bound by, an existing T cell in a patient
Data Source
AI summary
Disclosed is a new class of conjugated virus-like particles (VLPs). These conjugated VLPs bind a wide variety of tumors and comprise epitopes recognized by a prior T cell immune response already existing in a host. These epitopes are derived from pathogens or previous vaccinations (such as early childhood vaccines). This provokes the body's pre-existing cytotoxic immunity obtained through previous infection or previous childhood vaccination to be redirected to the tumor cells for the elimination of cancer, and form long-term anti-tumor immunity. The described conjugated VLPs are useful for tailoring a broad range of tumors towards a response from existing immunity circumventing the need to identify tumor antigens or generate tumor-specific immune responses. Importantly, the compositions and methods described herein broadens opportunities for treatment for all cancer types in subjects who previously had un-targetable cancers due to various technological and biological limitations of currently available immuno-therapeutic drugs.