Recombinant Antigen-Presenting Cells for Rare Immune Cell Expansion
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for cell-based immunotherapy face challenges in expanding populations of immune cells, particularly those representing a small fraction of the total cell population, such as NK cells and gamma/delta T cells, to sufficient numbers for therapeutic efficacy.
Innovation Solution
Recombinant antigen-presenting cells (RAPCs) engineered to express IL-21, OX40L, 4-1BBL, and IL-15 are used to isolate and expand immune cells ex vivo, enhancing their survival and expansion by acting as vehicles for delivering these cytokines and co-stimulatory molecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional antigen presenting cells are used to expand immune cells ex vivo, then the method is simple and easy to operate, but the expansion efficiency of rare immune cell populations (NK cells, gamma/delta T cells) is insufficient
Solution Approach 1:
The patent combines multiple cytokine expression functions (IL-21, IL-15, OX40L, 4-1BBL) into a single antigen presenting cell system. The RAPC simultaneously expresses all four cytokines through co-transfection or sequential transfection of plasmids, eliminating the need for multiple separate cytokine treatments and simplifying the overall expansion protocol while dramatically improving rare immune cell expansion efficiency
Solution Approach 2:
The engineered antigen presenting cell is designed to perform multiple functions simultaneously: it provides antigen presentation, secretes IL-21 for B cell and antibody responses, secretes IL-15 for NK cell activation and proliferation, expresses OX40L for T cell costimulation, and expresses 4-1BBL for additional T cell activation. This multi-functional RAPC system replaces what would otherwise require multiple separate components or treatment steps
2Productivity
If multiple cytokines are delivered separately to expand immune cells, then each cytokine can be optimized individually, but the process becomes complex and time-consuming
Solution Approach 1:
The antigen presenting cells are engineered for continuous, sustained secretion of multiple cytokines throughout the culture period. The cytokines are expressed from integrated or episomal plasmids that maintain stable expression over time, providing continuous stimulation to immune cells without requiring repeated medium changes or additions of fresh cytokines, thereby reducing culture time while maintaining high expansion rates
Solution Approach 2:
The cytokine expression capabilities are pre-installed in the antigen presenting cells through genetic engineering before the immune cell expansion begins. The RAPCs are prepared in advance with all necessary cytokine expression machinery in place, so when immune cells are added to the culture, they immediately receive all required cytokine signals without waiting for sequential additions
Data Source
AI summary
The present disclosure provides recombinant antigen presenting cells and methods of use thereof in the culture and expansion of immune cells ex vivo. In some aspects, immune cells expanded through co-culture of the recombinant antigen presenting cells disclosed herein are administered to a subject to treat a disease or condition in the subject, e.g., to treat a cancer.