Enhanced CAR T cell therapy offers new strategy for lymphoma
A new study from Penn Medicine marks a significant development in the ongoing evolution of CAR T cell therapy, as a novel cytokine-enhanced CAR T that has been tested in patients with blood cancer shows robust response rates.
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A next-generation “armored” CAR T cell therapy shows promising results in a small study of patients whose B-cell lymphomas continued to resist multiple rounds of other cancer treatments, including commercially available CAR T cell therapies. The new therapy diminished cancer in 81% of patients and resulted in complete remission in 52%, with some of the earliest patients treated experiencing durable remission for two years or more. The findings, in a study led by Jakub Svoboda, Carl June, and a team of researchers in the Perelman School of Medicine, are published in the New England Journal of Medicine.
While CAR T cell therapy—a personalized form of cancer immunotherapy first successfully developed by June and his team at Penn—has revolutionized treatment for many blood cancers, more than 50% of patients with lymphoma who receive currently available CAR T cell therapy do not experience a long-term remission.
“I’m thrilled that this new generation of CAR T cell therapy, created here at Penn, was highly effective in patients who have already tried everything available to treat their lymphoma,” says Svoboda, an associate professor of hematology-oncology, who led the clinical trial at Penn Medicine’s Abramson Cancer Center. “It’s also encouraging to see that the toxicity of this novel product was not different than what we already see with commercial CARs.”
When cancer continues to advance despite aggressive treatment, it’s due in part to immune suppression and T cell exhaustion that make anti-cancer therapies less effective.
To combat these challenges, a team led by June, the Richard W. Vague Professor in Immunotherapy, developed a new, “armored” CAR T cell product called huCART19-IL18. Like most other CAR T cell products for lymphoma, it targets a surface antigen called CD19. However, this version was further modified to secrete interleukin 18 (IL18), a pro-inflammatory cytokine capable of enhancing the immune system, by recruiting additional immune cells to support the engineered T cells. In doing so, it further protects the CAR T cells and promotes their ability to attack the cancer cells, says June.
By analyzing blood samples from patients after they received treatment, the research team found strong evidence indicating that adding IL18 to the CAR T cells contributed to the robust response rates. “Based on these results, we believe that incorporating cytokine secretion into CAR T cell design will have broad implications for enhancing cellular therapies, even beyond blood cancers,” says June. “With longer T cell persistence and expansion, this strategy could be powerful in settings where CAR T hasn’t performed as well, such as solid tumors.”
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