The immune system consists of various types of specialized cells. They have specific functions: some destroy cancer cells, some recognize antigens, and others suppress autoimmune reactions. However, obtaining these vital cells is difficult because they are primarily located deep within tissues.
Modern immunotherapy (e.g., CAR-T therapy) has proven revolutionary in hemato-oncology, yet it has shown less effectiveness against solid tumors. The main obstacle is that we cannot easily generate the required quantity and type of immune cells.
The solution lies in cell reprogramming. Through transcription factors (a kind of genetic “switch”), researchers can directly transform an ordinary cell (e.g., a fibroblast) into an immune cell. This method allows us to bypass the complex and lengthy process of transformation through stem cells. Such a direct path significantly simplifies the production of effective cellular therapy.
The Search for Immune Cell “Recipes”
Researchers at Lund University have created an innovative platform, REPROcode, which identifies the genetic “recipes” needed for cell reprogramming. Along with searching for combinations of transcription factors, the system determines their optimal dosage and timing of application.
The “Immune Library,” consisting of 408 transcription factors, is a unique resource for medicine. Through it, it becomes possible to create regulatory T-cells that suppress autoimmune reactions and “killer” cells directed against cancer. REPROcode lays the foundation for the era of programmable immunotherapy, which will allow doctors to create the cells the patient needs at the time they are needed.
To better understand how this technology will change the future treatment of cancer and autoimmune diseases, “Medscriptum” contacted one of the leading authors of the study, Professor Filipe Pereira of Lund University.
Immunotherapy currently helps some cancer patients but leaves many others behind. Which patient groups (those with cancer, autoimmune diseases, chronic infections) do you see benefiting most from REPROcode technology?
Immunotherapy has transformed cancer care, but many patients still do not benefit. Some immune cell types that could be used for an effective treatment are rare or difficult to obtain. Our work focuses on immune cell reprogramming, that converts readily accessible cells into specific immune cell types with therapeutic potential. REPROcode, described in our recent study, provides a systematic way to identify the molecular “recipes” needed to generate these cells.
The patients who stand to benefit most are those with cancers that do not respond to current immunotherapies including immune checkpoint inhibition or CAR-T cell therapies. By expanding the range of immune cells that can be generated and deployed, REPROcode opens new opportunities for treating resistant tumors. Importantly, the same approach could also be applied to autoimmune diseases, chronic infections, and transplantation, where precisely tuning immune responses, either boosting immunity or inducing tolerance, is critical.
Your research discovered remarkably simple “recipes” using just 3-5 transcription factors. How long does it take in the lab to make these immune cells ready for a patient? Could REPROcode manufacturing be significantly faster than existing cell therapies like CAR-T?
Our research shows that complex immune cell identities can be programmed using simple combinations of just 3–5 transcription factors. Once these “recipes” are defined, generating immune cells in the lab is relatively fast: reprogramming dendritic cells takes around nine days, and natural killer (NK) cells about twelve days. These timelines are comparable to current CAR-T cell manufacturing.
Where REPROcode is potentially transformative is not primarily in shortening manufacturing time, but in dramatically accelerating discovery. Existing approaches to develop new immune cell therapies are slow and largely trial-and-error, especially when identifying effective combinations of transcription factors. REPROcode systematically resolves these combinations, expanding the immune cell types that can be engineered and allowing new therapies to move toward development much more quickly.
Importantly, once these recipes are identified, they can be encoded into delivery systems and applied directly in vivo, enabling immune cells to be generated where they are most needed inside the patient. This opens the door to a broader and more scalable form of immune engineering, going well beyond today’s CAR-T therapies.
Treatment costs remain a major barrier for patients. Right now one CAR-T treatment costs hundreds of thousands. Could hospitals make REPROcode cells much cheaper? What’s realistic in 3-5 years?
Cost is one of the biggest limitations of current cell therapies like CAR-T, which rely on complex, personalized manufacturing outside the patient and can cost hundreds of thousands of dollars per treatment. A major advantage of reprogramming-based approaches is their potential to simplify this process dramatically.
Building on our work in dendritic cell reprogramming, we have shown that tumor cells can be converted into immune cells directly inside the tumor using gene delivery with adenoviral vectors. This in vivo strategy could function as an off-the-shelf immunotherapy, removing much of the manufacturing, logistics, and infrastructure that drive current costs. Importantly, early in vivo CAR-T approaches already suggest that costs could be reduced by more than ten-fold compared to conventional autologous CAR-T therapies.
REPROcode expands this potential even further by rapidly identifying minimal genetic “recipes” needed to generate many different immune cell types, which can then be deployed using similarly streamlined in vivo delivery strategies. In realistic terms, over the next 3–5 years we expect to gain a clear picture of how much costs can be reduced. Our first clinical trials testing in vivo reprogramming are planned for 2027 and will provide critical insight into feasibility, regulation, and scalability. While REPROcode-based therapies are unlikely to be inexpensive overnight, they have strong potential to be far more affordable than today’s cell therapies by simplifying both discovery and delivery.
You’ve successfully generated both dendritic cells and natural killer cells. Which immune cell type excites you most for helping patients, and why? What disease would you target first in clinical trials?
Dendritic cells excite me the most right now because they sit at the very center of the immune system: they decide whether an immune response is switched on, switched off, or reshaped. By reprogramming cells into dendritic cells directly inside tumors, we aim to trigger a coordinated, long-lasting anti-tumor immune response rather than targeting a single immune component.
Our first clinical focus is cancer, with in vivo dendritic cell reprogramming expected to enter clinical trials in patients with melanoma, head and neck cancer, and other tumors accessible to intratumoral administration. These are diseases where immune activation can be decisive, yet current immunotherapies still fail many patients. Looking ahead, I am equally excited about extending this technology to other immune cell types, including those with cytotoxic functions characteristic of natural killer cells, as well as regulatory dendritic cells, which could open new therapeutic avenues for autoimmune diseases.
Lastly, before we get too excited about REPROcode’s potential, what are the main practical hurdles to bringing REPROcode into clinical practice – manufacturing, regulation, safety, or others?
The biggest hurdles are not manufacturing alone, but safety, regulation, and validation at scale. Traditional cell therapies face major regulatory and logistical challenges because cells must be isolated, engineered outside the body, and reinfused into patients. Our move toward in vivo reprogramming was driven by the need to simplify this path and make translation more realistic.
For REPROcode specifically, the most demanding phase was building a comprehensive immune factor library, a technically complex and time-consuming effort that is now complete. The next challenges lie in rigorously testing the most promising reprogramming combinations in relevant disease models, ensuring precise control, safety, and reproducibility. These steps are essential to meet regulatory standards.
In short, the key hurdles ahead are demonstrating safety and effectiveness in patients and navigating regulatory approval, but by simplifying both discovery and delivery, REPROcode is designed to lower the barriers to clinical translation.
Source: Cell systems
