Breakthrough "Armoured" CAR T-Cell Therapy Shows Promising Results in Tough-to-Treat Lymphomas

CAR T-cell therapy revolutionized cancer treatment by using a patient’s own immune cells to target blood cancers. However, its impact has been limited by relapse and resistance, especially in B-cell lymphomas—where more than half of patients do not achieve lasting remission after receiving current FDA-approved therapies.

Researchers at Penn Medicine have developed a new, next-generation version of this therapy, called huCART19-IL18, designed to overcome these challenges. Unlike traditional CAR T cells, this “armoured” version not only targets cancer cells but also secretes interleukin-18 (IL18), a molecule that enhances immune activity and supports the engineered cells within the tumor microenvironment.

In a recently published phase 1 study in the New England Journal of Medicine, the results were highly encouraging. Among 21 patients with aggressive, treatment-resistant B-cell lymphomas, most of whom had received multiple prior therapies, including earlier-generation CAR T products, 81% experienced tumor shrinkage, and 52% achieved complete remission. Some patients have remained in remission for over two years, suggesting durable responses may be possible with this approach.

Importantly, the therapy did not introduce new or unexpected safety issues. Side effects such as cytokine release syndrome and neurotoxicity remained consistent with those observed in standard CAR T therapies and were manageable using existing treatment protocols.

The strategy behind huCART19-IL18 centers on boosting the immune system’s ability to sustain its attack on cancer cells. Like most other CAR T therapies for B-cell lymphoma, the engineered T cells are designed to recognize the CD19 protein found on malignant cells. What sets this therapy apart is its built-in production of IL18, a pro-inflammatory cytokine that helps activate and recruit other immune cells, reinforcing the overall immune response.

This addition appears to counteract common barriers to CAR T-cell effectiveness, such as immune suppression within the tumor environment and T-cell exhaustion. Early biological data collected during the study supports the idea that IL18 significantly contributed to the high response rates observed.

One of the other major innovations of the Penn team is a streamlined manufacturing process that reduces production time for the CAR T cells from the standard 9–14 days down to just three. For patients with fast-growing cancers, this shorter turnaround can make a critical difference, allowing treatment to begin before the disease progresses further. There’s also evidence that this quicker manufacturing timeline may improve the therapeutic potency of the T cells.

This study marks the first time a cytokine-enhanced CAR T-cell therapy has been tested in patients with blood cancer, and the implications extend well beyond lymphoma. The underlying concept, arming CAR T cells with immune-boosting cytokines, could be applied to other cancers, including those where CAR T therapies have historically shown limited success, such as solid tumors.

Building on these results, the researchers are preparing additional clinical trials, including studies targeting acute lymphoblastic leukemia and chronic lymphocytic leukemia. A trial for non-Hodgkin’s lymphoma using a similar IL18-enhanced CAR T product is already underway. Efforts are also ongoing to refine and scale the manufacturing process in partnership with a biotechnology spinout, with the goal of expanding access to these advanced therapies.

Beyond clinical outcomes, the data generated from this trial is providing valuable insight into how and why CAR T therapies fail in some cases, helping guide future improvements in treatment design and patient selection.

This therapy represents a significant step forward in the evolution of personalized cancer immunotherapy, offering new hope for patients with few remaining options, and potentially laying the groundwork for broader applications in oncology.