Multi-Cytokine Scaffold Strategy Produces Longer-Lasting CAR T Cells for Cancer and HIV

Albert Einstein College of Medicine researchers develop a manufacturing approach that generates immune cells capable of self-renewal, addressing a major limitation of current CAR T therapies

By Curie | Biotech Reporter

March 13, 2026 — A research team at Albert Einstein College of Medicine has developed a new strategy for engineering CAR T cells that could dramatically extend how long the therapies remain effective after infusion — a persistent challenge that has limited their use against both cancer and HIV.

The approach, described in a paper published in Science Advances, uses a specially engineered protein scaffold called HCW9206 that links three cytokines — IL-7, IL-15, and IL-21 — known to promote T cell survival and immune memory. When this multi-cytokine scaffold is used during manufacturing instead of the standard activation protocol, the resulting CAR T cells contain a much higher proportion of T memory stem cells, which are capable of self-renewal and can generate fresh waves of active immune fighters over time.

"The goal was to engineer therapeutic immune cells so they would not only be powerful killers but also long-lived and capable of self-renewal, to markedly extend their effectiveness after infusion into patients," said Harris Goldstein, MD, senior author and professor of pediatrics and microbiology & immunology at Einstein.

The persistence problem is significant. In roughly half of cancer patients treated with CAR T therapy, the engineered cells lose their potency over time and the cancer returns. The same issue has constrained efforts to use CAR T cells against HIV, where the goal is to eliminate infected cells that hide in long-lived reservoirs.

In mouse models of human leukemia, both conventional and multi-cytokine scaffold-generated CAR T cells eliminated cancer initially. But when researchers simulated relapse by re-infusing leukemia cells weeks later, only the multi-cytokine scaffold cells mounted a strong recall response and prevented tumor recurrence.

In a humanized mouse model of HIV, the engineered CAR T cells eliminated significantly more infected cells than conventionally manufactured cells — and CAR T cells generated from actual HIV patients using the new method also successfully eradicated infected cells.

"Now that we have shown that we can generate potent CAR T cells that are longer-lived, we may be able to reduce blood cancer relapse rates and improve long-term remission for cancer patients," Goldstein said. "For HIV, immune cells with this kind of staying power may one day help maintain viral control after stopping antiretroviral therapy, a critical step toward sustained drug-free remission and, potentially, a functional cure."

The scaffold was developed by HCW Biologics. The research was funded by the National Institutes of Health.