From immunology to engineering: Maksim Mamonkin’s path to designing “living drugs”

For most of his early career, Maksim (Max) Mamonkin was focused on understanding how the immune system works. Now, he’s designing new therapies that harness its power to fight cancer. 

Mamonkin, a scientist in pediatric hematology and oncology at Columbia and a member of the Columbia Initiative for Cell Engineering and Therapy (CICET), builds engineered T cells—living therapies designed to recognize and destroy cancer. The shift from studying immune cells to constructing them reflects a broader change in how he approaches science: moving from analyzing biological systems to designing them with a specific goal in mind. 

Trained as an immunologist, Mamonkin spent years studying how T cells function during infection and how those processes break down in disease. But over time, he found himself drawn less to the question of why the immune system fails and more to what could be done about it. That shift took shape during his postdoctoral and early independent work at Baylor College of Medicine, where he began working on engineered T-cell therapies, including chimeric antigen receptor (CAR) T cells—an emerging approach at the time that aimed to turn immune cells into targeted cancer treatments.

Designing around biology’s constraints

Much of Mamonkin’s early work focused on a fundamental challenge: how to use T cells to treat cancers that arise from T cells themselves. 

In these diseases, the same markers that identify cancer cells are often present on normal immune cells, raising the risk of “friendly fire.” Addressing that challenge required new approaches to engineering T cells—ones that could distinguish between harmful and healthy targets or adapt dynamically to different conditions. 

At Baylor University, work from his lab helped lay the foundation for multiple early-phase clinical trials of CAR-T in leukemia and lymphoma, with one of these experimental therapies now being evaluated in a national multi-center phase 2 trial in T-cell lymphoma. This translational work also contributed to a growing understanding of how engineered cells behave in patients and what is important to achieve optimal clinical activity, reinforcing a key idea that continues to shape his work: the most meaningful advances come not from a single breakthrough, but from continuous refinement and iteration.

"The process is the product”

At the center of that approach is a deeply collaborative model of science, one that Mamonkin sees as essential to moving complex therapies from concept to clinic. 

“The process is the product,” he says, citing the notion that cell manufacturing matters as much as engineering itself. And in cell therapy, that idea applies not just to how cells are manufactured, but to how the science itself is done. 

Developing a new therapy is not a linear process. It requires moving back and forth between the lab and the clinic—designing a concept, testing it in preclinical models, advancing it into trials, and then returning to the lab with new data to refine the next iteration. Each step introduces new questions, new constraints, and new opportunities for improvement. 

Mamonkin asserts that kind of iterative cycle depends on bringing together expertise from across disciplines. Clinicians help define the most urgent unmet needs and shape trial design. Manufacturing and regulatory teams determine how therapies can be produced safely and consistently. Computational scientists, engineers, and basic researchers contribute new tools and ways of thinking about the problem. 

“No single lab can do all of that,” Mamonkin says. “You need people who think differently and who bring different strengths to the table.”

Collaboration as infrastructure

At Columbia University Irving Medical Center, Mamonkin has found that model is not just possible; it’s built into the structure. As a member of CICET, led by Michel Sadelain, MD, PhD, Mamonkin is actively working across the Herbert Irving Comprehensive Cancer Center, department of pediatrics, and collaborating with Columbia investigators across engineering, genomics, immunology, and clinical oncology. “Being a part of the HICCC, CICET, and the broader Columbia community is a tremendous opportunity to do impactful science,” says Mamonkin.

Rather than building every capability within his own lab, he is intentionally designing a program that connects with groups across Columbia and beyond, leveraging specialized expertise in areas like genome editing, protein engineering, and computational design. He was recently named a Biohub Scholar, part of a broader network that brings together researchers across institutions to tackle ambitious challenges, including new approaches to early detection and prevention.

A focus on pediatric cancers

In his role as director of laboratory and translational research in the division of pediatric hematology, oncology, and stem cell transplantation, Mamonkin is leading efforts to develop new cell therapies for pediatric cancers, an area he describes as both high-impact and under-resourced.

While childhood cancers are relatively rare, they often lack effective treatment options, particularly in relapsed or refractory cases. And because the patient population is smaller, there is less commercial incentive to develop new therapies. 

“That’s where academic centers can make a difference,” he says. “If you can develop something that brings a child back to a normal life, the impact is enormous.” 

His group is focusing on some of the most challenging diseases, including brain and solid tumors and difficult-to-treat leukemias, while also working to improve outcomes in cancers where cell therapy is already used.

Expanding cell therapy’s newest frontiers

Despite its promise, cell therapy still faces significant limitations. While CAR T cells have shown remarkable success in certain blood cancers, their effectiveness in solid tumors remains limited by barriers such as poor tumor infiltration, immune suppression, and toxicity. 

Addressing those challenges is a central focus of Mamonkin’s work. His lab is exploring new targets, refining cell designs, and developing approaches that could make therapies more precise, more durable, and safer. Many of these advances are being driven by rapid progress in related fields, from genome editing to protein engineering to artificial intelligence, opening new possibilities for how these therapies can be designed and optimized. 

At the same time, he is thinking about how to make these treatments more accessible. Current CAR T therapies are complex, highly individualized, and often prohibitively expensive. 

One potential solution is the development of “off-the-shelf” therapies, engineered cells that can be produced in advance and delivered more quickly and at lower cost. Mamonkin notes that this could also expand access globally, particularly in areas where the highly specialized labs currently needed for engineered cell therapies are nonexistent.

A turning point for cell therapy

For Mamonkin, the field is entering a new phase, where ideas that once seemed out of reach are becoming increasingly feasible. 

“It’s an exciting time,” he says. “You can think about something that sounds almost like science fiction. Now there’s a real chance you can actually make it happen.”