Engineered T Cells for HIV Viral Load Control
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Solution Overview
Problem
Current therapies are ineffective in treating chronic viral infections such as HIV, as they fail to adequately control or clear the virus due to impaired cytotoxic T lymphocyte responses, and there is a lack of recombinant human progenitor cells and engineered T cells that can effectively target viral antigens.
Innovation Solution
Development of recombinant human progenitor cells transduced with vectors encoding T cell receptors specific for viral epitopes, which differentiate into engineered human thymocytes and T cells capable of recognizing and responding to viral antigens, thereby enhancing the immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ex vivo generated CTLs are administered to HIV infected individuals, then the CTL response is augmented, but the cells become dysfunctional due to HIV infection and ongoing viral-induced pathology
Solution Approach 1:
The patent applies preliminary action by generating CTLs with enhanced functionality and resistance properties before administering them to HIV-infected patients. The ex vivo expansion and selection processes prepare the cells in advance to withstand the hostile viral environment, ensuring they remain functional upon infusion rather than becoming dysfunctional like conventional CTLs.
Solution Approach 2:
The patent employs parameter changes by modifying critical parameters of the CTLs during ex vivo expansion, including cytokine exposure (IL-2, IL-7, IL-15, IL-21), activation status, and selection criteria. These parameter modifications transform ordinary CTLs into enhanced cells with improved survival, proliferation, and functional capacity in the presence of HIV.
2Reliability
If the virus is placed under selective pressure by the CTL response, then the CTL response controls viral load, but the virus mutates to escape immune surveillance
Solution Approach 1:
The patent applies dynamics by creating a dynamic, evolving CTL response that adapts to viral mutations. The continuous ex vivo expansion and re-infusion of enhanced CTLs, along with poly-specific targeting of multiple HIV epitopes, creates a moving target that can track and respond to viral evolution rather than being outmaneuvered by it.
Solution Approach 2:
The patent employs universality through poly-specific CTLs that target multiple HIV epitopes simultaneously. This multi-functionality ensures that even if the virus escapes one CTL specificity through mutation, other CTL specificities remain effective, maintaining broad viral load control despite viral adaptability.
3Adaptability or versatility
If autologous CTLs are used for treatment, then the cells are specific to the patient's immune system, but the cells are ineffective due to HIV infection
Solution Approach 1:
The patent applies self-service by using the patient's own immune cells (autologous CTLs) that have been enhanced ex vivo. The cells serve themselves by maintaining their autologous compatibility while acquiring enhanced functional properties through external cytokine exposure and selection, eliminating the need for allogeneic cells while overcoming the ineffectiveness problem.
Data Source
AI summary
Disclosed herein are recombinant human progenitor cells, engineered human thymocytes, and engineered human T cells. The recombinant human progenitor cells are made by transducing a human hematopoietic stem cell with a vector having a nucleic acid molecule which encodes a human T cell receptor specific to a virus, such as Human Immunodeficiency Virus, or an epitope thereof. The recombinant human progenitor cells differentiate and mature into the engineered human thymocytes and the engineered human T cells. Also disclosed herein are methods of inhibiting, reducing or treating a viral infection in a subject, such as a human subject, which comprises administering recombinant human progenitor cells, engineered human thymocytes, and/or engineered human T cells to the subject.