19 December 2022

Early research into re-treatment with CAR-T therapy has found the approach to be safe, delegates to the 2022 American Society of Hematology Annual Meeting have heard.

A team from the University of Pennsylvania’s Abramson Cancer Center presented preliminary results of an ongoing phase I clinical trial. The trial concluded that patients whose non-Hodgkin’s lymphoma (NHL) had relapsed after CAR-T therapy could be re-treated successfully with huCART19-IL18, a novel fourth-generation CAR-T treatment.

It is the first clinical trial in the USA with anti-CD19 CAR-T cells secreting interleukin 18 (IL-18).

Senior author and CAR-T pioneer Dr Carl June said: “We designed an ‘armoured’ CAR that secretes IL18 and tested it in mice, where we found it to have potent antitumor efficacy in our preclinical studies.”

All seven patients who received huCART19-IL18 responded to the therapy, including individuals who previously did not respond to or relapsed following treatment with commercial CAR-T cell therapies.

Four had a complete response and remained cancer-free after three months, while three had a partial response. All patients are alive at a median follow-up of eight months.

Lead author Dr Jakub Svoboda, associate professor of haematology-oncology at Penn, said: “Although these are preliminary results, it’s encouraging to see how well these patients have done.”

The study enrolled patients with CD19+ relapsed/refractory NHL or chronic lymphocytic leukaemia (CLL), who had received at least two lines of therapy, including CAR-T therapy.

The study is continuing to increase the dose of huCART19-IL18 and will enrol patients one at a time until the team determines the appropriate dose.

Because there is a three-day manufacturing time, huCART19-IL18 can be ready to administer faster than CAR-T products, which have a manufacturing time of nine to 14 days.


The conference also heard from Dana-Farber Cancer Institute researchers, who showed that the CAR-T therapy axicabtagene ciloleucel (axi-cel) is safe for people with lymphoma in the brain or spinal cord.

They said the therapy shows encouraging signs of efficacy in a small pilot trial involving patients with primary or secondary CNS lymphoma.

A subsequent in-depth, molecular study of individual CAR-T cells isolated from patients’ blood and cerebrospinal fluid (CSF) showed a surprising difference between the two CAR-T-cell populations: the cells in the CSF display a molecular signature that indicates activation of the interferon pathway, an important step in rallying the immune system.

Dr Caron Jacobson, who led the patient trial, said: “For many patients with lymphoma of the central nervous system, there aren’t great treatment options. Our early results suggest that expanding the applicability of CAR-T cells to this indication could improve patient outcomes.”

Source: ASH December 2022



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