Cell therapy has fundamentally changed what is possible in cancer treatment. CAR T-cell therapies have shown that a patient’s own immune cells can be collected, genetically engineered to recognize cancer and returned to the body as a living medicine. For some patients with advanced blood cancers, these therapies have produced responses after other treatment options have failed. But the same personalization that helped make the first generation of CAR T possible also creates one of the field’s greatest challenges. Traditional autologous CAR T therapy begins with cells collected from an individual patient. Those cells must be transported, engineered, expanded, tested and returned to the treatment center before they can be infused. The process can take weeks and requires complex manufacturing and logistics.

For more than a decade, researchers have asked a different question: What if these powerful medicines could be designed from the beginning to reach more patients? The manufacturing and engineering answers are only now catching up.

Across the Biocom community, companies are approaching that challenge from multiple directions. Some are creating standardized therapies that can be manufactured in advance. Others are programming cells with increasingly sophisticated functions. And a new generation of in vivo approaches aims to generate therapeutic cells directly inside the patient.

Together, these innovations are beginning to redefine cell therapy as a more scalable, programmable and potentially accessible therapeutic platform.

Building Cell Therapies in Advance

One of the clearest ways to simplify cell therapy is to move away from manufacturing a unique product for every patient. Researchers are developing allogeneic, or donor-derived, therapies that can be produced in larger batches, stored and made available when needed. The concept brings cell therapy closer to a conventional pharmaceutical model, while introducing scientific challenges around consistency, persistence and immune rejection.

San Diego-based Fate Therapeutics is approaching the problem through induced pluripotent stem cells, or iPSCs. Rather than repeatedly sourcing cells from individual patients or donors, Fate develops engineered iPSC master cell banks that can serve as renewable starting material for standardized cell therapies. The platform allows the company to incorporate multiple genetic modifications before creating the master cell bank, potentially enabling consistent production of highly engineered T-cell and natural killer cell therapies.

Fate is applying the approach across cancer and autoimmune disease. Its oncology pipeline includes FT836, an off-the-shelf CAR T-cell therapy now in Phase 1 trials, where early results have shown tumor reduction in heavily pretreated patients with metastatic colorectal cancer. The broader promise is a fundamentally different manufacturing model: one engineered cell source capable of producing many therapeutic doses. Bay Area-based Caribou Biosciences is pursuing the same goal through precision genome editing. The company uses its CRISPR-based technology to develop donor-derived CAR T cells that can be manufactured in advance. Its lead programs include two off-the-shelf therapies: one CD19-directed for B-cell non-Hodgkin lymphoma, the other BCMA-targeted for multiple myeloma, both incorporating genetic edits designed to help the cells function despite immune barriers.

Caribou’s work illustrates an important point: making cell therapy scalable is not simply about manufacturing larger batches. The cells themselves must be engineered to survive, persist and perform outside the individualized autologous model.

Programming Cells to Make Better Decisions

Scale is only one part of the next generation of cell therapy. Researchers are also developing ways to give engineered cells more precise instructions. That challenge is particularly important in solid tumors, where many promising targets are also present on healthy cells and where tumors can be highly heterogeneous.

Greater Los Angeles-based A2 Biotherapeutics is developing logic-gated cell therapies intended to help engineered T cells distinguish malignant cells from normal tissue. Its Tmod platform combines activating and blocking mechanisms. The approach is designed to recognize a cancer-associated target while also detecting genetic information that helps determine whether a cell is healthy or malignant. Rather than instructing a T cell to simply attack whenever it encounters a particular target, the platform gives it additional biological information before it acts. A2 Bio is initially applying this strategy to solid tumors, including lung, colorectal, pancreatic and other cancers.

South San Francisco-based Senti Bio is taking the concept further through programmable gene circuits. Its lead CAR-NK therapy, aimed at acute myeloid leukemia, incorporates multiple genetic instructions, including an “OR” gate designed to recognize either of two cancer-associated targets and a “NOT” gate intended to protect certain healthy cells. In effect, the engineered cells can interpret multiple biological signals before determining how to respond.

This represents a broader shift in cellular engineering. Instead of programming immune cells with a single target, researchers are beginning to build increasingly complex decision-making systems into the cells themselves.

As this logic-gating approach matures, researchers, may extend it to recognize additional signal combinations, helping engineered cells respond more selectively to disease.

Moving the Cell Factory Inside the Patient

Off-the-shelf approaches could simplify external manufacturing. But another emerging strategy asks whether much of that manufacturing needs to happen outside the body at all. In vivo cell therapy aims to deliver genetic instructions directly to immune cells inside the patient. If successful, the approach could eliminate several steps that currently define CAR T treatment, including collecting cells, transporting them to a manufacturing facility, engineering and expanding them externally, and shipping the finished therapy back to the treatment center.

Seattle-based Umoja Biopharma is among the companies advancing this concept into clinical development. Its VivoVec platform uses engineered viral particles to deliver genetic instructions to T cells inside the body, causing those cells to generate their own CARs. Rather than manufacturing CAR T cells externally and infusing the completed product, the treatment is designed to create them directly in the patient.

Umoja is developing in vivo CAR T programs across several hematologic cancers, including therapies directed at CD19 and CD22, and is exploring additional targets in multiple myeloma. The approach could ultimately transform CAR T from a customized cell-manufacturing process into something closer to an injectable genetic medicine.

Fellow Seattle-based Sana Biotechnology is pursuing in vivo cell engineering through a different delivery platform. Sana is developing targeted fusosomes designed to deliver genetic material to specific immune cells and convert them into CAR T cells inside the body. Its programs include in vivo CAR T candidates for non-Hodgkin lymphoma and multiple myeloma.

The potential implications are significant. If immune cells can be reliably engineered inside the patient, cell therapy could eventually require less specialized manufacturing infrastructure and potentially reach treatment settings far beyond today’s major cell therapy centers.

The approach is still early, and questions around delivery, safety, control and durability remain. But it represents one of the field’s most ambitious attempts to rethink how cellular medicines are produced.

A New Definition of Scalability

The first generation of cell therapies demonstrated that living cells could become powerful medicines. The next generation is asking how broadly that concept can be applied.

Fate Therapeutics is developing renewable iPSC-derived therapies designed for off-the-shelf use. Caribou Biosciences is using genome editing to create standardized allogeneic CAR T cells. A2 Biotherapeutics and Senti Bio are adding increasingly sophisticated biological logic to help therapeutic cells make more selective decisions. Umoja Biopharma and Sana Biotechnology are pushing the concept further by attempting to generate CAR T cells directly inside patients.

Each approach addresses a different limitation, but together they reveal a common trajectory. Cell therapy is becoming less defined by where a patient’s cells begin and more defined by what scientists can program those cells to do.

That evolution could reshape manufacturing, distribution and treatment delivery. Off-the-shelf therapies could reduce the need to manufacture a unique product for each patient. More sophisticated engineering could allow cells to recognize increasingly complex disease biology. In vivo approaches could eventually eliminate significant portions of the external manufacturing process altogether.

None of these strategies eliminates the scientific complexity of cellular medicine. Standardized cells must overcome immune barriers. Logic-gated therapies must reliably interpret biological signals. In vivo systems must deliver genetic instructions to the right cells while maintaining precise control.

But solving those challenges could help determine whether cell therapy remains a highly specialized treatment model or evolves into a platform capable of reaching a much broader population. Across the Biocom community, that next generation is already taking shape. The future of cell therapy may remain highly personalized in what it achieves for each patient.

Increasingly, however, it may no longer need to be bespoke in how it is made.