Engineered NK Cells for Solid Tumor Immunotherapy
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Solution Overview
Problem
Current cancer treatments, such as adoptive cell therapies, face limitations in targeting solid tumors and hematologic malignancies due to short half-life and poor proliferation of unmodified NK cells, leading to ineffective cancer cell targeting and limited supply for immunotherapy.
Innovation Solution
Engineered NK cells are developed with heterologous polypeptides like IL-15 and hypo-immunity regulators (PD-L2, TGF-beta, CD46, CD55, CD59) to enhance persistence, resistance against immune rejection, and cytotoxic activity, derived from induced pluripotent stem cells (iPSCs) for targeted cancer therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If unmodified NK cells are used in adoptive cell therapy, then the treatment can be administered, but the cells exhibit short half-life and poor proliferation leading to ineffective cancer targeting
Solution Approach 1:
The NK cells are engineered to autonomously produce IL-15 through heterologous polypeptides, enabling self-service for their own persistence and proliferation without requiring external cytokine support, thereby resolving the short half-life issue while maintaining targeting effectiveness
Solution Approach 2:
The patent modifies the biological parameters of NK cells by introducing heterologous polypeptides that alter cytokine production capabilities, transforming the cells from short-lived to persistent while maintaining their cytotoxic function against cancer cells
2Quantity of substance
If unmodified NK cells are used, then the therapy can proceed, but the supply of viable NK cells for immunotherapy is limited
Solution Approach 1:
By engineering NK cells to autonomously produce IL-15, the cells serve themselves for proliferation and expansion, dramatically increasing the supply of viable NK cells without requiring continuous external cytokine administration
Solution Approach 2:
The heterologous polypeptides are introduced into NK cells during ex vivo expansion, preparing the cells in advance with enhanced proliferation capabilities before administration, ensuring sufficient supply for effective therapy
3Reliability
If engineered NK cells with heterologous polypeptides are used, then persistence and resistance to immune rejection are enhanced, but the device complexity increases
Solution Approach 1:
Multiple functions are merged into single heterologous polypeptide constructs that simultaneously provide IL-15 production and immune evasion capabilities, reducing overall system complexity while achieving multiple therapeutic goals
Solution Approach 2:
The engineered NK cells possess universal multi-functionality, combining cytotoxic activity, autonomous proliferation, persistence, and immune rejection resistance in a single cell type, simplifying the therapeutic approach despite increased cellular complexity
Data Source
AI summary
The present disclosure describes systems and methods for immunotherapies Immune cells can be engineered to exhibit enhanced half-life as compared to control cell (e.g., a non-engineered immune cell). Immune cells can be engineered to exhibit enhanced proliferation as compared to a control cell. Immune cells can be engineered to effectively and specifically target diseased cells (e.g., cancer cells) that a control cell otherwise is insufficient or unable to target. The engineered Immune cells disclosed herein can be engineered ex vivo, in vitro, and in some cases, in vivo. The engineered Immune cells that are prepared ex vivo or in vitro can be administered to a subject in need thereof to treat a disease (e.g., myeloma or solid tumors). The engineered Immune cells can be autologous to the subject. Alternatively, the engineered immune cells can be allogeneic to the subject.