A groundbreaking advancement in cancer treatment has emerged from the collaboration between Sant Pau Research Institute (IR Sant Pau), Sant Pau Hospital, and the Josep Carreras Leukaemia Research Institute. Researchers have developed HSP-CAR30, an innovative form of CAR-T cell therapy targeting the CD30 protein. This therapy demonstrated exceptional efficacy during a Phase I clinical trial, with findings published in the prestigious journal Blood. The study involved patients suffering from refractory CD30+ lymphomas, including Hodgkin lymphoma, where conventional treatments often fail. The results highlighted not only a 100% overall response rate but also significant complete remission rates, accompanied by minimal adverse effects. These outcomes underscore the potential of HSP-CAR30 to transform the landscape of lymphoma treatment.
The development of HSP-CAR30 represents a milestone in addressing the challenges posed by refractory CD30+ lymphomas. Historically, these cancers have proven difficult to treat due to the limited persistence of modified cells and high relapse rates. To overcome these obstacles, researchers at IR Sant Pau employed advanced genetic engineering techniques to optimize CAR-T therapy. A key innovation involves targeting a more stable region of the CD30 protein, preventing tumor cells from evading detection by shedding fragments into the bloodstream. Additionally, the manufacturing process incorporates interleukin-21 (IL-21) alongside IL-7 and IL-15, promoting the expansion of long-lived memory T cells. This ensures sustained effectiveness over time, offering patients prolonged protection against disease recurrence.
The Phase I clinical trial provided compelling evidence supporting the efficacy and safety of HSP-CAR30. Conducted on ten patients with relapsed or refractory classical Hodgkin lymphoma or CD30+ T-cell lymphoma, the trial achieved remarkable results. Under the leadership of Dr. Javier Briones, Head of Haematological Oncology and Transplant Research Group at IR Sant Pau, the study revealed a 100% overall response rate among participants. Moreover, 50% experienced complete remission, characterized by undetectable signs of the disease through imaging studies and clinical analyses. Crucially, 60% of patients who attained complete remission remained disease-free after a median follow-up period of 34 months. Such durability underscores the lasting impact of CAR-T cells within the body.
From a safety standpoint, HSP-CAR30 exhibited a favorable profile throughout the trial. No dose-limiting toxicities were observed, and adverse effects such as Grade 1 cytokine release syndrome (CRS) were mild and manageable. Notably, none of the patients developed neurotoxicity, further reinforcing the feasibility of this therapy for broader clinical application. Another significant finding was the high in vivo persistence of CAR30+ cells, detectable in 60% of evaluable patients one year post-infusion. During peak T cell expansion, central memory T cells (TCM) and stem-like memory T cells (TSCM-LIKE) predominated, directly correlating with treatment efficacy and longevity.
HSP-CAR30 marks Europe's first successful CAR-T30 study completion, presenting immense promise for future developments. As Dr. Ana Caballero, Consultant Haematologist and co-investigator of the trial, emphasized, selecting the CD30 epitope and preserving less differentiated T cells ex vivo could revolutionize refractory CD30+ lymphoma treatment. Expanding upon these findings, the ongoing Phase II trial has already treated 32 patients, with an additional 10 included to strengthen data robustness. Preliminary results indicate that over 55% of participants achieved complete remission, bolstering hopes for improved outcomes in larger cohorts.
This pioneering research would not have been possible without substantial support from various organizations and foundations. Key contributors include the Josep Carreras Leukaemia Foundation and the Josep Carreras Leukaemia Research Institute, which acquired critical equipment and funded drug production for initial patients. Additional backing came from La Marató de TV3, Carlos III Health Institute, ‘La Caixa’ Foundation, Agency for the Management of University and Research Grants (AGAUR), Network of Advanced Therapies (RICORS), and the Blood and Tissue Bank (BST). Together, these entities have facilitated significant advancements in CAR-T therapy, bringing renewed hope to countless individuals facing limited treatment options.
The success of HSP-CAR30 heralds a new era in combating refractory CD30+ lymphomas. By optimizing CAR-T therapy to ensure both immediate and enduring effectiveness, researchers have paved the way for transformative medical breakthroughs. With continued support and expanded trials, this innovative approach holds the potential to significantly improve patient outcomes, offering a beacon of hope in the fight against aggressive forms of cancer.