Universal Antigen Presenting Cells for NK Cell Expansion
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Solution Overview
Problem
Existing methods struggle to generate clinically sufficient quantities of optimally functional natural killer (NK) cells for cancer immunotherapy, and there is a need to develop stringent controls to prevent unintended cytotoxicity and autoimmunity.
Innovation Solution
Engineering universal antigen presenting cells (UAPCs) to express CD48, CS1, and membrane-bound interleukin-21 (mbIL-21) and 41BB ligand (41BBL) to expand NK cells, which are derived from leukemia cells and optimized for NK cell activation and tumor targeting.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional antigen presenting cells are used to expand NK cells, then NK cell quantity can be increased, but the functional optimality and clinical sufficiency of expanded NK cells cannot be achieved
Solution Approach 1:
The patent segments the antigen presenting cell into multiple functional components: (1) base APC providing structural framework, (2) mbIL-21 providing cytokine stimulation, (3) 41BBL providing costimulatory signal, (4) CD48/CS1 providing adhesion and activation signals. This segmentation allows each component to be optimized independently while working synergistically to produce clinically sufficient quantities of optimally functional NK cells.
Solution Approach 2:
The patent creates a composite antigen presenting cell by combining multiple transgenic elements (mbIL-21, 41BBL, CD48, CS1) into a single engineered APC. This composite structure integrates diverse functional properties that collectively enhance NK cell expansion and functionality, achieving both quantity and quality requirements for clinical immunotherapy.
2Strength
If NK cells are activated to enhance killing power, then cytotoxicity against tumors increases, but unintended cytotoxicity and autoimmunity may occur
Solution Approach 1:
The engineered APC provides localized and controlled activation signals through specific surface molecules (CD48, CS1, 41BBL, mbIL-21) that interact with corresponding receptors on NK cells. This localized signaling ensures activation occurs only at the APC-NK cell interface under controlled conditions, enhancing tumor cytotoxicity while minimizing off-target effects and autoimmunity.
3Productivity
If antigen presenting cells are engineered with multiple transgenes, then NK cell expansion and functionality improve, but device complexity increases
Solution Approach 1:
The patent merges multiple transgenic elements (mbIL-21, 41BBL, CD48, CS1) into a single engineered APC line, allowing simultaneous delivery of multiple activation signals from one cell type. This consolidation simplifies the overall system architecture compared to using multiple separate APC populations or complex culture conditions, while achieving log-scale NK cell expansion with optimal functionality.
Data Source
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AI summary
Provided herein are universal antigen presenting cells. Also provided herein are methods of expanding immune cells using the UAPCs and methods for the treatment of a disease, such as cancer, using the expanded immune cells.