Persistence Therapeutics developing implantable immunotherapy device

A new Research Triangle company, Persistence Therapeutics, is developing a small, implantable device that generates and delivers genetically engineered T cells directly inside the body.

These cells, called chimeric antigen receptor T cells or “CAR-T cells,” are currently administered as a personalized immunotherapy for certain blood cancers but require time-intensive and costly manufacturing.

In recent years, preclinical and early clinical studies have shown that it is possible to generate CAR-Ts within a patient’s own body, or “in vivo,” circumventing external manufacturing and providing significant advantages in treating blood cancers such as leukemia and multiple myeloma.

However, enabling CAR-T therapy to work effectively in solid tumors, which present significant physical and immunologic barriers, has remained a major challenge. Persistence’s Synthnode is designed to address this limitation and expand the reach of CAR-T therapy into solid tumors.

The North Carolina Biotechnology Center recently awarded Persistence, a North Carolina State University and University of North Carolina at Chapel Hill spin-out, its largest-ever one-time Strategic Growth Loan of $650,000. NCBiotech previously awarded the technology a 2019 Flash Grant of $24,000 to support proof-of-concept research.

Addressing significant unmet needs

Erin Kaltenbrun, Ph.D., and Kathy Meserve, director and senior director, respectively, of NCBiotech’s Emerging Company Development group, evaluate companies for investment and support company development through mentorship and connections with prospective funders and partners. They worked closely with the Persistence team to evaluate the technology for the Strategic Growth Loan.

“The Persistence technology addresses several significant unmet medical needs, including speed of treatment, cost of production, and improving patient access to life-saving cancer treatment,” Meserve said.

Blood Cancer United estimated 192,000 new blood cancer diagnoses (leukemia, lymphoma, or myeloma) were made in 2025, while an estimated 1.7 million people, or 9.1 percent of all people with cancer, are living with or in remission from blood cancers. These cancers often have few early symptoms, meaning they are diagnosed later in the disease process, making them more difficult to treat.

Improving current CAR-T delivery

Persistence seeks to improve significantly on the production and delivery of existing CAR-T cancer immunotherapy. First approved for clinical use by the Food and Drug Administration in 2017, seven CAR-T therapies have been approved by the FDA.

CAR-T therapy is currently administered to patients with blood cancers who have not responded well to other treatments. The lengthy treatment process begins with a blood draw to obtain the patient’s T cells. These T cells are then sent to a laboratory where they are genetically modified to express a specialized receptor at the cell surface. This receptor, referred to as the “CAR,” enables the T cell to recognize and destroy cancer cells. After these modified T cells, or CAR-Ts, are expanded, they are shipped back to the hospital and infused back into the patient. (Click here for National Cancer Institute CAR-T graphic.)

Drawbacks to traditional CAR-T

CAR-T therapy has had many successes, curing blood cancers in some patients, while putting others’ cancers into remission. However, there are serious drawbacks that limit widespread adoption:

• Lengthy process. The CAR-T manufacturing process, “from vein to vein,” can take two to four weeks—time that many critically ill cancer patients do not have. 
• High cost. The complex manufacturing process makes this an expensive therapy, costing about $450,000 per patient. 
• Difficult access. The need for specialized manufacturing facilities generally means patients need to live near or be able to travel to a large medical center to receive treatment.
• Limited applicability. Conventional and other in vivo CAR-T therapies have not been very effective in treating solid tumors.
• Safety concerns. Some patients can experience serious side effects due to the body’s response to a rapid influx of activated T cells.

Dime-size ‘cell manufacturing facility’

The Persistence approach leverages a dime-sized sponge-like scaffold that acts as a synthetic lymph node (Persistence calls its implant a “Synthnode”) that can be inserted surgically via a minimally invasive procedure. The Synthnode, with activating biologics, is loaded with a mixture of patient cells and viral particles containing the specialized CAR and then implanted into the patient. The implant begins producing and releasing CAR-Ts almost immediately.

Importantly, in experimental models, Synthnode CAR-Ts have been shown to persist in circulation longer than conventionally generated CAR-Ts, which may serve to prevent tumor recurrences. As Persistence advances through its remaining preclinical studies, support from NCBiotech, together with funding from Jupiter Bioventures, is accelerating the company’s path toward IND submission and first-in-human studies.    

“The development of an in-body CAR-T factory, where a small implant serves as the container for CAR-T generation, versus complex off-site manufacturing, collapses the entire CAR-T treatment paradigm into a simple therapy,” Kaltenbrun said.

This innovative approach could offer patients noteworthy advantages: 

• Shorter time to treatment. The time from when the patient’s T cells are obtained to the time of CAR-T administration (“vein to vein”) is less than a day. 
• Reduced cost. In vivo CAR-T avoids the need for complex, expensive manufacturing. Persistence estimates that production and delivery of its Synthnode will be less than a third of the cost of current CAR-T solutions.
• Solid tumor application. Early preclinical studies suggest that Synthnodes are more effective at killing solid tumors than conventional CAR-T.
• Improved patient safety profile. Synthnodes release CAR-T cells gradually over time rather than all at once, which is anticipated to reduce safety concerns.

Expanding the reach of CAR-T into solid tumors

While CAR-T therapies have transformed outcomes in certain blood cancers, their impact in solid tumors has been far more limited. Solid tumors create physical and biological barriers that make it difficult for engineered immune cells to reach the tumor, persist long enough to be effective, and remain active in an environment designed to suppress immune attack. As a result, many promising CAR-T approaches have struggled to translate their success in hematologic malignancies into solid tumor settings.

Synthnode is designed to change that dynamic. Rather than relying on systemically infused cells to overcome the physical and immunologic barriers of solid tumors, the approach generates and activates CAR-T cells locally by implanting the device at or near the tumor site. By generating cells at the source, this strategy aims to enhance expansion, improve persistence, and promote a more durable anti-tumor response—while potentially reducing systemic toxicity.

Unlocking CAR-T therapy for solid tumors, which account for the majority of all cancers, represents the company’s primary strategic objective. If successful, this approach could open the door to treating a much wider range of cancers and significantly expand the impact of CAR-T therapy.

Outstanding leadership, research team

Persistence is led by an interdisciplinary team with expertise that spans oncology, biomaterials, and clinical science. “We have great confidence in the Persistence team,” Meserve said.

Part of that confidence comes from a familiar name: Ned Sharpless, M.D., who chairs the company’s board of directors. He is a former director of the National Cancer Institute and Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill. Sharpless also co-founded Jupiter Bioventures, a “biotech foundry” that has committed significant seed funding to Persistence, meeting the NCBiotech loan’s matching investment requirement.

Charles Buchen, M.D., the company’s chief executive officer, has a successful track record in biotech, with prior senior roles in building innovative companies and advancing novel therapeutics from early development through clinical and financing milestones.

Persistence scientific co-founders include Pritha Agarwalla, Ph.D., now the company’s vice president of research and from whose postdoctoral research the technology was conceived; Yevgeny Brudno, Ph.D., associate professor at UNC’s Eshelman School of Pharmacy and the Lampe Joint Department of Biomedical Engineering; and Gianpietro Dotti, M.D., professor of microbiology and immunology at the UNC School of Medicine.      

Exciting company, strong community support

Buchen is excited about Persistence. “It has been incredible to work with the company’s scientific founders,” he said. Buchen also credited NCBiotech with supporting emerging companies such as Persistence.

“I have been impressed by NCBiotech’s extensive support, not only through funding, but through their commitment to integrating us into this amazing community,” he said. “We have been able to bring together Persistence founders with leaders across the academic and life sciences communities to advance our novel therapy for cancer patients,” he added.

The future: strong CAR-T business growth

On the national level, in vivo CAR-T immunotherapies are generating a lot of attention among investors and biopharma companies. In 2025, in vivo CAR-T companies raised more than $3.3 billion and saw over $6 billion in strategic acquisitions. The global in vivo CAR-T therapy market is projected to reach $30.64 billion by 2033, according to one report.

Given this outlook and the compelling preclinical results they’ve observed, Buchen feels optimistic about the company’s future.

The company hopes to enter clinical trials by 2027. To get there, Persistence still needs to complete IND-enabling work, including preclinical toxicology, and scale up its manufacturing process for the Synthnode.

Through it all, Buchen and the Persistence team remain focused on their overarching goal: to lay the foundation for an in vivo CAR-T therapy platform that is scalable, accessible, and more effective across diverse patient populations, while expanding CAR-T therapy into solid tumors, where effective treatment options remain limited.