Virus-Specific CAR T Cells Targeting CD30 for Hematologic Malignancies
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Solution Overview
Problem
The widespread adoption of CAR T cell therapies for hematologic malignancies is hindered by manufacturing failures, disease progression before infusion, and high costs, as well as the risks of graft-versus-host disease (GVHD) and allorejection associated with off-the-shelf T cell products from unrelated donors.
Innovation Solution
Development of virus-specific immune cells, such as Epstein-Barr virus-specific T cells, engineered with chimeric antigen receptors (CARs) targeting CD30, which include an antigen-binding domain specific to CD30, a transmembrane domain derived from CD28, and a signaling domain with an immunoreceptor tyrosine-based activation motif (ITAM), to selectively target and eliminate alloreactive T cells and cancer cells without causing GVHD.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If off-the-shelf CAR T cell products from unrelated donors are used, then accessibility and cost are improved, but graft versus host disease (GVHD) and allorejection occur
Solution Approach 1:
The patent converts the harmful alloreactive T cells into beneficial anti-tumor effectors by engineering them with CARs. The same T cells that would normally cause GVHD are redirected to target CD30-positive tumor cells, transforming the harmful alloreactivity into a therapeutic advantage for treating hematologic malignancies
Solution Approach 2:
The patent modifies the functional parameters of allogeneic T cells by introducing chimeric antigen receptors that change their target specificity from self-reactive to tumor-reactive. This parameter change allows the cells to maintain their proliferative and cytotoxic capabilities while redirecting them against cancer cells rather than host tissues
2Loss of time
If allogeneic CAR T cells are administered, then immediate availability is improved, but rejection by recipient alloreactive T cells occurs
Solution Approach 1:
The patent transforms the harmful effect of recipient alloreactive T cells (which would normally reject allogeneic infusions) into a beneficial mechanism for eliminating tumor cells. The recipient's alloreactive T cells are engineered to recognize and kill CD30-positive tumor cells, converting the rejection response into an anti-tumor response
Solution Approach 2:
The patent creates universally applicable CAR T cell products that can be used across multiple recipients without manufacturing customization. The allogeneic CAR T cells are designed to function effectively in any recipient by targeting the universal CD30 antigen on tumor cells, enabling immediate availability while maintaining therapeutic efficacy
3Reliability
If autologous CAR T cells are manufactured, then specificity to patient's immune system is improved, but manufacturing failure and disease progression occur
Solution Approach 1:
The patent prepares CAR T cell products in advance from healthy donor cells before the patient needs treatment. These pre-manufactured allogeneic CAR T cells are stored and can be immediately administered to patients, eliminating the lengthy autologous manufacturing process while maintaining therapeutic effectiveness through targeted CD30 recognition
Data Source
AI summary
Treatment and prevention of cancer using virus-specific immune cells, comprising a chimeric antigen receptor (CAR) or nucleic acid encoding a CAR, wherein the CAR comprises: (i) an antigen-binding domain which binds specifically to CD30, (ii) a transmembrane domain, and (iii) a signalling domain, wherein the signalling domain comprises: (a) an amino acid sequence derived from the intracellular domain of CD28, and (b) an amino acid sequence comprising an immunoreceptor tyrosine-based activation motif (ITAM), is disclosed.