CAR-T – chimeric antigen receptor T-cell – therapy is a type of immunotherapy specifically developed for each individual patient and involves genetically reprogramming the patient's own immune system cells to express specific chimeric antigen receptors (CAR) on the cell surface, which are then reinfused to the patient to target and attack tumor cells.
"CD19-directed T-cell therapies have produced unprecedented therapeutic responses in several B-cell malignancies. However, traditional CAR-T cell manufacturing requires a lengthy culturing process including ex-vivo T-cell expansion, leading to a door-to-door turnaround time of around twenty to twenty-five days. For patients with particularly aggressive tumors this is simply too long to wait," said Pere Barba, Head of Advanced Therapies at the Vall d'Hebron University Hospital's Hematology Department and Hematologist and Lead Investigator of VHIO's Experimental Hematology Group, and first author of this present study, results of which he presented today at the 67th American Society of Hematology Annual Meeting (ASH 2025).
Another limitation is that the process of rapidly amplifying the CAR-T cell population requires them to divide a lot and very quickly. By the time these cells reach the patient they are therefore exhausted, which can compromise their efficacy.
CAR-Ts in 48 hours
"The T-Charge™ next generation platform does not require the expansion phase and thus reduces the CAR-T cell manufacturing time to under two days. In addition, since the CAR-T cells are not exposed to cytokines for so long, they are less exhausted and more effective," added Barba.
Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is a fast-growing cancer of the bone marrow and blood. It is the most common childhood cancer, but it also affects adults. While first-line treatment achieves a cure rate of between 50 to 60% in adult patients, those who relapse have a very poor prognosis. There is therefore an unmet clinical need to investigate and develop more effective therapies for this patient population.
Phase 1 study in adult patients with relapsed or refractory B-cell ALL
A phase 1 multicenter study was designed to evaluate the safety and efficacy of rapcabtagene autoleucel, an innovative CD 19-directed CAR-T Cell therapy that is rapidly manufactured using the T-Charge™ platform, in 41 previously treated patients with relapsed or refractory B-ALL who received single-infusion rapcabtagene autoleucel at targeted dose level. The treatment showed a manageable safety profile and promising antitumor activity.
The best overall response of complete remission (CR) or complete remission with incomplete recovery of blood count at three months, meaning that the disease had completely disappeared or the disease had disappeared but abnormal levels of blood cells were still detected, was 70% in patients who received the lowest dose (DL1), 100% with second lowest dose (DL2), 92% with the third (DL3), and 83.3% in patients who received the highest dose (DL4).
The median duration of response (DOR) was 5.3 months for DL1 and 10.8 months for DL2, and not reached for DL3 or DL4.
"Results from this study demonstrate that CAR-T therapy with rapcabtagene autoleucel showed an acceptable balance of safety, efficacy, and cellular expansion. Also considering the reduced production time using the T-Charge™ platform, our findings support further investigations evaluating this therapy and translating this approach into routine clinical practice," concluded Pere Barba.
