CAR T-cell therapies have substantially advanced cancer treatment, but they face a critical challenge: many patients relapse after achieving complete remission. Dana-Farber Cancer Institute researchers have devised a promising strategy to overcome this issue.

The work, published recently in Nature Biotechnology, describes a novel technique for improving the efficiency and lifetime of CAR T cells. The novel technique, known as the CAR-Enhancer (CAR-E) therapeutic platform, promises to keep CAR T cells active longer while also allowing them to maintain cancer cell memory. This breakthrough has the potential to prevent relapse by keeping the cells watchful against cancer recurrence.

"CAR T-cell therapies have been a breakthrough treatment for B-cell hematologic cancers such as B-cell leukemias, lymphomas, and multiple myeloma," according to the study's senior author, Mohammad Rashidian, PhD. "In myeloma, for example, nearly all patients respond well to CAR T-cell treatments at first, but almost all relapse, half within one to two years of treatment." The relapse coincides with the disappearance of CAR T-cells in the bloodstream."

The researchers redirected their focus from altering CAR T cells to creating an external answer. The researchers developed the CAR-E platform by combining a weaker form of the immunological signaling molecule interleukin-2 (IL-2) with the antigen against which CAR-T cells are directed. This technique targets CAR T cells while minimizing damage to regular T cells.

"The CAR-E therapy not only causes CAR T cells to proliferate but to diversify—to generate different types of CAR T cells with different properties," Rashidian told me. "It generated not only effector T cells, which most patients already have, but also stem cell-like memory T cells, central memory T cells, and effector memory T cells—a complete repertoire of the kinds of T cells needed for an effective immune response to cancer."

CAR-E treatment has demonstrated excellent results in laboratory cultures and animal models, including total tumor elimination. The technique also has other advantages, such as potentially reducing the number of CAR T cells required and mitigating associated concerns like cytokine release syndrome.

Taha Rakhshandehroo, PhD, the study's first author, stated that the most exciting aspect of this therapy is its easy integration into the care of patients receiving CAR T-cell therapies. "It's a very elegant answer to the problem of CAR T-cell depletion. "We're excited to start clinical trials."

The forthcoming clinical trials will evaluate the safety, dose, and administration schedule of CAR-E therapy, with an initial treatment phase beginning around a month following CAR T-cell infusion.