Draper device equips CAR T-cell therapy developers with a streamlined bioprocessing method designed to lower cost, improve efficiency and broaden patient access
CAMBRIDGE, MA—Immunotherapy has emerged as the hottest trend in cancer care by creating “living drugs” that are able to recognize and kill a patient’s cancer cells without damaging healthy cells. Making those therapies, however, is cumbersome, slow and expensive. For instance, the process for developing CAR T-cell therapies involves gathering T cells from the cancer patient’s blood, re-engineering them in a lab so they will recognize cancer cells as an “enemy” and then reintroducing these enriched T cells to the patient’s body. The current price tag for a single treatment: $450,000. The timeframe: 12-17 days.
“Even with 20 companies working on CAR-T treatments, and three marketed products and additional promising candidates on the way, there needs to be a better approach to T-cell therapy bioprocessing,” said David O’Dowd, associate director of biomedical solutions at Draper. “The production of these powerful treatments must be standardized, scaled and automated to enable them to be produced efficiently, safely and at a more affordable cost to make them accessible to more patients.”
In addressing this challenge, engineers at Draper have developed a microfluidic transduction device (MTD) to enable companies to manufacture T-cell therapies with half of the viral vector required by many current approaches. One of the main factors driving the prohibitive expense of CAR T-cell therapies is the cost of the viral vector, which serves as the delivery vehicle of genomic materials into specific cells. Viral vectors, which can account for as much as 75 percent of a treatment’s cost, are themselves difficult and costly to manufacture.
As a single device that accomplishes cell preparation and enrichment, Draper’s MTD can be integrated easily into existing lab automation systems for generating CAR T-cells. The MTD uses transmembrane fluid flow to both concentrate and co-localize target cells with viral vectors. Because this device increases the vector concentration in the vicinity of the cells, the result is greatly improved transduction efficiency. How much improvement? Draper scientists tested the platform and found they could achieve a twofold increase in viral transduction efficiency of human T-cells following a 90-minute transduction versus a 24-hour static control—meaning, MTD needed only half as much viral vector to reach the same transduction efficiency in comparison to current approaches.
“Increasing the efficiency of viral transduction or reducing the amount of required virus has the potential to dramatically lower the cost of manufactured cell therapies and enable broader clinical use,” said Ken Kotz, a senior member of the technical staff in Draper’s biomedical solutions group. “We are able to do both with Draper’s MTD device. We believe that implementation of this technology at the clinical level will significantly reduce costs associated with transduction during the manufacturing of cell therapies.”
According to Jenna Balestrini, a program manager of cell bioprocessing and biomedical solutions at Draper, the MTD proved itself similarly effective in two additional areas valued by cell therapy companies: enhancing transduction in other primary human cells such as stem cells, and permitting the use of non-lentiviral vectors. “The technology provides the control, precision and ability to scale to a higher throughput system that could potentially handle up to 1B cells,” said Balestrini.
The microfluidic transduction device is part of an integrated portfolio of resources at Draper intended to help government, industry and academia make better use of biomedicine. The company is working with pharmaceutical companies on drug discovery and development; medical device developers to provide clinicians with quantitative diagnostic data at bedside to help them diagnose their patients’ illnesses more accurately and quickly; and biomanufacturing companies on increasing the speed and reducing the cost of processing cell therapies.
Draper has designed and developed microelectronic components and systems going back to the mid-1980s. Our integrated, ultra-high density (iUHD) modules of heterogeneous components feature system functionality in the smallest form factor possible through integration of commercial-off-the-shelf (COTS) technology with Draper-developed custom packaging and interconnect technology. Draper continues to pioneer custom Microelectromechanical Systems (MEMS), Application-Specific Integrated Circuits (ASICs) and custom radio frequency components for both commercial (microfluidic platforms organ assist, drug development, etc.) and government (miniaturized data collection, new sensors, Micro-sats, etc.) applications. Draper features a complete in-house iUHD and MEMS fabrication capability and has existing relationships with many other MEMS and microelectronics fabrication facilities.
Draper’s Biomedical Solutions capability centers on the application of microsystems, miniaturized electronics, computational modeling, algorithm development and image and data analytics applied to a range of challenges in healthcare and related fields. Draper fills that critical engineering niche that is required to take research or critical requirements and prototype or manufacture realizable solutions. Some specific examples are MEMS, microfluidics and nanostructuring applied to the development of wearable and implantable medical devices, organ-assist devices and drug-delivery systems. Novel neural interfaces for prosthetics and for treatment of neurological conditions are being realized through a combination of integrated miniaturized electronics and microfabrication technologies.
Draper continues to develop its expertise in designing, characterizing and processing materials at the macro-, micro- and nanoscales. Understanding the physical properties and behaviors of materials at these various scales is vital to exploit them successfully in designing components or systems. This enables the development and integration of biomaterials, 3D printing and additive manufacturing, wafer fabrication, chemical and electrochemical materials and structural materials for application to system-level solutions required of government and commercial sponsors.