KSHV-Specific T Cell Expansion via Antigen-Presenting Cells
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Solution Overview
Problem
Current therapies for Kaposi sarcoma-associated herpesvirus (KSHV) infections are limited in effectively clearing the virus and establishing lasting immunity, particularly in immune-compromised individuals, and there is a lack of understanding of immunodominant KSHV-specific T cell epitopes crucial for targeted antiviral immunity.
Innovation Solution
Development of a pharmaceutical composition comprising KSHV-specific T cells derived from naïve T cells that have not been exposed to KSHV antigens, stimulated using mature antigen-presenting cells and specific cytokines, to produce cytokines like IFNγ and TNFα upon exposure to KSHV antigens, enabling targeted immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies (antiviral, radiation, chemotherapy) are used to treat KSHV infections, then some therapeutic effect is achieved, but they fail to establish lasting immunity and have appreciable toxicities
Solution Approach 1:
The patent uses antigen-presenting cells as intermediaries to present KSHV antigens to naïve T cells, enabling the development of KSHV-specific T cell products that provide lasting immunity without the toxicities of conventional therapies
Solution Approach 2:
The patent harnesses the patient's own immune system by expanding KSHV-specific T cells from their own naïve T cells, allowing the body to fight the infection itself rather than relying on external toxic therapies
2Reliability
If adoptive T cell therapy is developed using KSHV-specific T cells, then targeted immune response is achieved, but the complexity of characterizing immunodominant epitopes increases
Solution Approach 1:
The patent performs preliminary characterization of immunodominant KSHV-specific T cell epitopes before developing the therapeutic product, identifying key epitopes that will be used to stimulate naïve T cells and ensure targeted immune response
Solution Approach 2:
The patent extracts and focuses on specific immunodominant epitopes from the entire KSHV proteome, using only the most relevant epitopes for T cell stimulation rather than attempting to address the full complexity of the virus
3Quantity of substance
If T cell responses are assessed against whole KSHV proteome, then comprehensive coverage is achieved, but T cell responses against critical oncoproteins remain weak or absent
Solution Approach 1:
The patent applies local quality by focusing T cell stimulation on specific critical oncoproteins (v-FLIP, v-CYCLIN, v-GPCR, v-IL6, vIRF-3) rather than attempting uniform coverage of the entire proteome, ensuring strong responses against the most immunogenic and clinically relevant antigens
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 approach allows for the expansion of KSHV-specific T cell products from virus-naïve donors, enhancing immune responses against KSHV-associated cancers and providing a potential allogeneic T cell therapy and vaccine design for improved treatment and prevention of KSHV-related diseases.
Implementation Method 1
contacting a mature antigen-presenting cell that expresses or presents the KSHV antigen or epitope thereof
Implementation Method 2
The KST has been exposed to, presented with, and/or stimulated by the KSHV antigen or epitope thereof in the presence of one or more cytokines conductive to antigen presentation and stimulation of T cells
Data Source
AI summary
The invention described herein provide Kaposi Sarcoma-Associated Herpesvirus (KSHV) oncoprotein antigens and epitopes for expanding antigen-specific T cells. Such expanded T cells are useful for, e.g., in allogeneic or “off-the-shelf” adoptive T cell therapy.