Dendritic cell generator
Inventors
Murthy, Shashi K. • Collier, Bradley B.
Assignees
Northeastern University Boston
Publication Number
US-12157901-B2
Publication Date
2024-12-03
Expiration Date
2036-06-29
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Abstract
Devices, systems, and methods can be used for the automated production of dendritic cells (DC) from dendritic cell progenitors, such as monocytes obtained from peripheral blood. The invention makes it possible to obtain sufficient quantities of a subject's own DC for use in preparing and characterizing vaccines, for activating and characterizing the activation state of the subject's immune response, and to aid in preventing and/or treating cancer or infectious disease.
Core Innovation
The invention provides devices, systems, and methods for the automated production of dendritic cells (DCs) from progenitor cells, such as monocytes obtained from peripheral blood. The invention enables isolation of monocytes from a subject's blood and their conversion into dendritic cells in a fluidic device, allowing patient-specific DC generation. Methods of the invention utilize an automated process, including perfusion-based cell culture chambers with monocyte-binding surfaces, to simplify and reduce the time required for DC generation compared to prior manual approaches.
A core feature of the invention is the integration of a dendritic cell differentiation cassette containing a monocyte-binding substrate, a fluid inlet port, and a fluid outlet port, all coupled to enable controlled flow of culture medium for cell differentiation and maturation. The system further comprises reservoirs for culture medium and effluent, as well as pumps for automated fluid movement. The process binds monocytes directly in the cassette, differentiates them into DCs through cytokine exposure, and facilitates maturation, minimizing the need for manual manipulation and reducing usage of expensive reagents.
The invention addresses the need for automated, scalable, and cost-effective methods to generate sufficient quantities of patient-specific DCs. Traditionally, DC generation from monocytes required numerous manual steps, large blood volumes, and multiple transfers, which were labor-intensive and inefficient. The invention overcomes these limitations by enabling direct capture, differentiation, and maturation of DCs in an integrated and potentially disposable device, with possibilities for remote and parallel operation. This supports various uses including vaccine preparation, immune response characterization, and therapeutic interventions.
Claims Coverage
The patent includes multiple independent claims that define several inventive features related to automated dendritic cell generation systems and associated methods.
Automated dendritic cell generation system with integrated fluidics
A system comprising: - One or more dendritic cell differentiation cassettes with a plastic body, a cell culture chamber featuring a monocyte-binding substrate, and fluid inlet and outlet ports configured to allow flow of culture medium across the substrate. - A culture medium reservoir fluidically coupled to the cassette's inlet port. - A fluid collection reservoir fluidically coupled to the cassette's outlet port. - A pump configured to transfer fluid sequentially from the culture medium reservoir through the cell culture chamber and into the fluid collection reservoir.
Dendritic cell differentiation cassette construction
A dendritic cell differentiation cassette comprising: - A plastic body containing a cell culture chamber with a monocyte-binding substrate. - A fluid inlet port and a fluid outlet port, fluidically coupled to the chamber and configured for culture medium flow.
Method of preparing dendritic cells using the automated system
A method comprising: 1. Providing a liquid sample containing monocytes of a subject to the automated dendritic cell generation system (as described above). 2. Pumping the liquid sample into the cell culture chamber so that monocytes bind to the monocyte-binding substrate. 3. Pumping a dendritic cell differentiation medium into the chamber, leading to monocyte differentiation into dendritic cells and detachment from the substrate. 4. Optional further steps: pumping a maturation medium for dendritic cell maturation and collection of mature dendritic cells.
These inventive features collectively establish an automated, integrated fluidic system and associated cassettes and methods for the efficient and scalable generation of dendritic cells from blood-derived monocytes.
Stated Advantages
The methods and devices of the invention are simple and efficient, reducing costs of expensive reagents such as cytokines and cell culture media to a minimum.
The invention enables the automated, scalable, and patient-specific generation of dendritic cells with minimal user intervention, minimizing manual steps.
Compared to prior art, the process is shorter and less labor-intensive, allowing generation of about 10-fold more dendritic cells per milliliter of blood.
The integrated system supports large-scale or simultaneous processing of samples from several subjects, improving throughput and flexibility.
A direct binding and differentiation approach eliminates multiple transfers and purifications, improving DC yield and purity.
Documented Applications
Preparation and characterization of vaccines using patient-derived dendritic cells.
Activation and characterization of the subject’s immune response, including T cell response assessment.
Aiding in the prevention and/or treatment of cancer or infectious diseases using generated dendritic cells.
Preparation of dendritic cell vaccines for human use, including expansion of epitope-specific T cells.
Optimization and testing of dendritic cell differentiation and maturation protocols from monocytes or other dendritic cell progenitors.
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