ICML 2023 | HuCART19-IL18 in patients with lymphoma previously relapsed/refractory to anti-CD19 CAR-T therapy

So we realized that there is a great unmet need for patients with relapsed lymphoma who are progressing or who were failed by current anti-CD19 CAR-T therapies. So there is a need to develop better CAR-T products and also have therapies for the patients who do not get into long-term remissions from the current CAR-Ts. So our group at the University of Pennsylvania, under the leadership of Dr. Carl June, developed what we refer to as a fourth generation CAR-T, which is in many ways similar to the prior CAR-T products in a way that it can be very specific and can be specific in terms of the receptor to get to the tumor. But the enhancement is that this fourth generation or armored CAR-T can also secrete IL-18, which is a cytokine that may have properties that can enhance the proliferation of the CAR-T as well as the cytolytic potential. It may also have some anti-lymphoma properties. And so again, the combination of the CAR-T receptor on these cells and the ability to express IL-18 is very attractive. And so this was a first-in-human trial that used this product. We’ve treated now 13 patients as of March 2023, and we’ve seen some very encouraging results. First, we found that this is a feasible strategy because we’re able to manufacture these cells, it’s fairly safe. Again, the class effect, like the CRS or neurotoxicity, seems to be somewhat in line with the current second-generation T-cell products. And the efficacy, again, was surprisingly very high. We had a response rate over 80% with 55% of patients achieving complete response, and again, these appear to be durable. So we have now some patients going almost two years in remission even though previously they failed prior CAR-Ts. So again, we’re encouraged by that. We’re doing plenty of correlative studies in this study. So, you know, we will have information on tumor biopsies, cytokine levels, expansion levels. But again, these are ongoing and we probably need bigger numbers to make more sense of these. And yeah, so we’re continuing this project. We now have three cohorts, one in CD19 positive lymphomas, one in CLL and one in ALL. And so we’re expanding this trial and hope to get more patients, more information.