New findings from
Penn Medicine suggest that treatment with a novel “armored” chimeric antigen receptor (CAR) T-cell therapy may be effective at low cell doses in patients with lymphoma following the failure of previous anti-CD19 CAR T-cell therapy. The researchers published results from the small, phase 1 trial last week in the
New England Journal of Medicine.
The investigational product, huCART19-IL18, is an autologous anti-CD19 CAR T-cell therapy engineered to secrete interleukin-18 (IL-18), a pro-inflammatory cytokine. This enhancement is designed to recruit additional immune cells, boost T-cell function and potentially overcome immune suppression commonly seen in patients who have recieved multiple previous treatments.
The trial enrolled 21 adults who had received a median of seven prior therapies. All but one had previously received a commercially available CD19-directed CAR T-cell therapy. Patients received a single infusion of huCART19-IL18 (at one of five different dose levels) following lymphodepleting chemotherapy.
Notably, the product was manufactured using a three-day process developed by Penn’s Center for Cellular Immunotherapies, considerably shorter than the standard nine to 14 days. This accelerated timeline enabled patients with rapidly progressing disease to begin treatment more quickly.
At three months, 81% of patients had a partial or complete response, and 52% achieved complete remission. Several patients remained in remission for more than two years after treatment.
The toxicities observed in the trial were consistent with those typically seen in other CAR T-cell therapies, such as cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). These side effects were closely monitored and effectively managed by the clinical team. No new or unexpected safety concerns arose during the course of the study.
“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,” said Jakub Svoboda, MD, an associate professor at Penn Medicine and the study’s lead author. “It’s also encouraging to see that the toxicity of this novel product was not different than what we already see with commercial CARs.”
Additionally, the research team analyzed blood samples from patients post-treatment and found strong evidence that the inclusion of IL-18 in the CAR T cells played a significant role in the observed robust response rates. Researchers noted that these findings provide the first clinical evidence supporting the use of cytokine-secreting CAR T-cell therapy in blood cancer, with the potential to improve outcomes in relapsed disease and possibly extend to other indications.
“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,” said Carl June, MD, a co-author of the study and a pioneering researcher in the field of cell therapy. “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.”
The research team is currently planning clinical trials to expand huCART19-IL18 to patients with acute lymphocytic leukemia and chronic lymphocytic leukemia.
