Therapeutics

A New Strategy to Sustain CAR T‑Cell Activity and Improve Long‑Term Cancer Outcomes

A new protein enhancer developed at Dana-Farber could help CAR T-cell therapies remain active long enough to eliminate every cancer cell, preventing relapse and improving the potential for long-term remission.

A new therapeutic platform developed by Mohammad Rashidian, PhD, at the Dana‑Farber Cancer Institute has the potential to reshape the future of CAR T‑cell therapy. CAR T cells—immune cells engineered to recognize and attack cancer—can be remarkably effective, but they often lose activity before eliminating every last malignant cell. Because even a tiny number of surviving cancer cells can eventually regrow and cause the disease to return, complete clearance is essential. Rashidian and his team have created a protein “enhancer” that helps CAR T cells stay active far longer than they normally would, enabling full tumor eradication in preclinical models where relapse is otherwise expected.

“We’ve found a way to help CAR T cells stay active until they truly eliminate 100 percent of the tumor cells,” Rashidian says. “If this translates to patients, it could be a game changer.”

Why Sustaining CAR T‑Cell Activity Matters

CAR T‑cell therapy has transformed treatment for several blood cancers, often producing rapid and dramatic tumor reduction. But its biggest limitation is durability. After an intense initial burst of activity, CAR T cells can become exhausted and disappear from the body. When that happens, any remaining cancer cells—sometimes just a microscopic population—can begin to grow again. The longevity of CAR T‑cell activity is therefore just as important as the strength of the initial response.

Our hope is that this approach will help patients achieve durable responses—potentially even cures.
Mohammad Rashidian, MD

This is where Rashidian’s enhancer could make a meaningful difference. By preventing exhaustion and extending how long CAR T cells remain functional, the platform aims to eliminate not only the bulk of the tumor but also the small, treatment‑resistant pockets of disease that typically drive relapse. If CAR T cells can stay active long enough to finish the job, the likelihood of long‑term remission—and potentially cure—could increase significantly.

“Our hope is that this approach will help patients achieve durable responses—potentially even cures,” Rashidian says. “That’s the goal that drives this work.”

How the Enhancer Works

To address the durability challenge, Rashidian’s team developed a therapeutic protein that prevents CAR T cells from entering an exhausted state. Instead of burning out after the initial wave of tumor killing, CAR T cells treated with the enhancer remain active for months, continuing to patrol the body and eliminate residual cancer cells.

This effect has been demonstrated in a series of rigorous animal studies, including patient‑derived xenograft models of multiple myeloma, lymphoma, and leukemia. In these models, human cancer cells and human CAR T cells are introduced into mice, allowing researchers to observe how engineered T cells behave in a living system. CAR T cells supported by the enhancer persisted, remained functional, and continued to kill cancer cells until the tumors were completely eradicated. In models where relapse is typically expected, the treated animals remained disease‑free.

The team is now extending the platform to solid tumor models such as sarcoma, melanoma, glioblastoma, and pancreatic cancer—areas where CAR T‑cell therapies have historically struggled. Early findings suggest the enhancer may help engineered T cells resist exhaustion in these more immunosuppressive environments, opening the door to new therapeutic possibilities for patients with solid tumors.

Building the Scientific Foundation

Rashidian’s enhancer platform is supported by a growing body of preclinical research. In 2024, his team reported in Nature Biotechnology that the enhancer could boost CAR T‑cell proliferation, sustain their activity, and promote long‑lived memory formation in mouse models of multiple myeloma. The enhanced CAR T cells cleared tumors more effectively and remained active long after standard CAR T cells typically fade.

A follow‑up study published in 2026 in the Journal for Immunotherapy of Cancer expanded these findings across additional tumor models and developed a lead CAR-Enhancer candidate for clinical translation in multiple myeloma. Early experiments in solid tumor models also suggested that the enhancer may help engineered T cells resist exhaustion in more immunosuppressive environments.

Together, these studies provide a strong scientific rationale for advancing the enhancer platform into first‑in‑human testing. Funding from the Dana-Farber Cancer Institute Innovation Research Fund, the International Myeloma Society and Riney Foundation, the Blavatnik Therapeutics Challenge Awards, and the Parker Institute for Cancer Immunotherapy has been instrumental in supporting the project’s early development. Additional resources are being sought to accelerate the launch of the initial clinical trial.

A Platform With Broad Potential

Although the first clinical application will focus on multiple myeloma, the enhancer is designed as a modular technology that can be paired with many CAR T‑cell constructs. Rashidian envisions a future in which this platform can be applied broadly across hematologic malignancies and solid tumors, as well as next‑generation engineered T‑cell therapies.

“We are very hopeful about what this can mean for patients,” he stresses.

Team Members: Mohammad Rashidian, PhD, Nikhil Munshi, MD, Omar Nadeem, MD, Adam Sperling, MD, PhD, Kai Wucherpfennig MD, PhD

Team Members

A New Strategy to Sustain CAR T‑Cell Activity and Improve Long‑Term Cancer Outcomes

Mohammad Rashidian, PhD

Nikhil Munshi, MD

Omar Nadeem, MD

Adam Sperling, MD, PhD

Kai W. Wucherpfennig, MD, PhD