Accelerating pace of engineered cell therapies, from lab to bedside

Massachusetts Institute of Technology

What if a cancer patient could receive life-saving cellular therapy within days of diagnosis rather than weeks? What if pharmaceutical researchers could bring new treatments to market in months rather than years?

Kytopen is significantly speeding up both discovery and delivery of engineered cell therapies with its transformative Flowfect platforms. The MIT spinout was co-founded by associate professor of mechanical engineering Cullen Buie and former MIT research scientist Paulo Garcia, now the company’s CEO.

Cellular engineering is the process of enhancing or providing new capabilities to living cells, and producing these enhanced cells at scale for therapeutic purposes. Groundbreaking therapies for infections, genetic diseases, and many cancers rely on engineered cells, but the process of creating them can be slow and costly.

Delivery of genetic material into cells can be done virally, an effective but often prohibitively expensive method. Non-viral delivery methods are more accessible, but traditionally there is a compromise between cell viability and delivery efficiency. And as Garcia and Buie learned during an intensive customer discovery bootcamp in 2015, the time-consuming, highly manual process of non-viral cell manufacturing is a source of frustration for everyone in the business of developing, delivering, and receiving engineered cellular therapies.

Armed with this understanding of market and patient needs, the Kytopen team set about developing the Flowfect platform to help speed the cell engineering process. After all, Buie says, “A lab therapy isn’t a therapy until it’s delivered to patients.”

Flowfect combines mechanical energy from fluid flow and electrical energy from pulses to make cell membranes more permeable, Garcia explains. This enables minimally disruptive introduction of genetic material – RNA, DNA, or CRISPR Cas RNP – into the cytoplasm or nucleus of the cells in a continuous process. Experiments have shown higher cell viability and delivery efficiency with Flowfect than with traditional transfection methods while retaining cell functionality for downstream therapeutic applications.

While pursuing his PhD at Virginia Tech, Garcia produced pioneering research in the use of electric fields to kill solid tumors in the brain. Meanwhile at MIT, Buie’s bioengineering lab was advancing research in microfluidics and experimental fluid mechanics. It was Garcia’s mentor in Virginia who connected the two, recommending Garcia as a postdoc in Buie’s lab.

Their complementary expertise and research interests soon laid the groundwork for what would become Kytopen’s Flowfect platforms. “Fast forward a couple of years to MIT,” Garcia says, “where we are using electric fields not to kill cells, but to deliver genetic material into cells in order to give them the capability of performing enhanced therapeutic functions.”

In the lab, the 96-well Flowfect Array is compatible with commercially available liquid handling systems, which makes the technology more accessible to smaller labs and startups. In a therapeutic setting, Flowfect Tx uses a peristaltic pump and cartridge system to deliver a continuous flow of engineered cells. Both devices use the same underlying technology, enabling a smooth transition from lab to clinic. This doesn’t just mean a shorter scale-up timeline, it eliminates scaling from the timeline entirely.

The strength of the Kytopen team isn’t rooted only in their engineering and entrepreneurial talents, but also in an authentic, active commitment to diversity and inclusion. Buie points to the story of Onesimus, an enslaved man in colonial Boston who introduced methods of inoculation – widely practiced throughout Africa and among enslaved communities – that helped mitigate a deadly smallpox outbreak. Even more lives would have been saved had more white Boston leaders been willing to learn from African medicine.

“Who knows how many cures have been lost due to racial inequalities,” Buie says. Collaborators and colleagues who represent a range of life experiences and backgrounds are not just at the table, but involved at all levels of planning and decision-making, helping to ensure that Kytopen won’t make similar mistakes.

Garcia also highlights the community-building aspects of The Engine, the early-stage venture firm conceived and propelled out of MIT, as key to Kytopen’s early successes. “We are extremely blessed to be one of the first seven companies to have received investment from The Engine,” he says. In addition to funding, The Engine offers access to shared facilities, mentorship, and relationship-building with other entrepreneurs and industry partners. “We have built a community that is supporting each other and helping accelerate progress toward meaningful impact, not just in the biosciences,” Garcia says, “I would encourage anyone in the tough tech ecosystem to apply.”

Kytopen is currently focused on the growing field of immunotherapy-an area that ties closely to Garcia’s personal research interests. But the technology has potential in many fields, including vaccine development. Early in the Covid-19 pandemic, Garcia notes, Kytopen scientist James Hemphill was able to identify parameters that achieve high transfection efficiency and high cell viability of primary B-cells, part of the body’s immune system.

Given the many challenges of delivering genetic material into these delicate cells, it’s no surprise that Kytopen has piqued the interest of potential collaborators around the world. “What we’re looking for,” Garcia says, “are therapeutic partners or academic pioneers that have access to genetic material that can help accelerate the potential treatment of disease by leveraging our non-viral delivery methodology.”

Among Kytopen’s research goals in the coming year is to look closely at challenges in engineering CAR-T cells, a promising therapy for blood cancers like leukemia and lymphoma.

CAR-T cells use DNA as the genetic payload and that DNA can be toxic to the cells. “If we had access to therapeutically relevant DNA, we would start by investigating that toxicity issue and see if, with our platform, we can generate impactful results with low concentrations of DNA,” Garcia says.

Garcia’s PhD research produced exciting results in minimally invasive treatments for brain tumors. “I look forward to the day in which Flowfect engineered cell therapies actually treat brain tumors in human patients,” he says, bringing together his biomedical engineering expertise and his entrepreneurial goals.

Enabling and accelerating new cures for cancer? Flowfect could be the tool that makes it happen and it’s exactly the kind of world-changing tech fostered at MIT through The Engine. “Yeah, just a minimal goal,” Garcia laughs, “I don’t want to aim too high.”

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