A novel CAR-T cell therapy targeting the CD30 protein has demonstrated exceptional efficacy in patients with refractory CD30+ lymphoma, achieving a 100% overall response rate in a Phase I clinical trial. This groundbreaking treatment, developed by researchers at the Sant Pau Research Institute (IR Sant Pau) in collaboration with Sant Pau Hospital and the Josep Carreras Leukaemia Research Institute, represents a significant advancement in the treatment of these challenging malignancies.
The innovative therapy, known as HSP-CAR30, has shown remarkable ability to promote the expansion of memory T cells, leading to long-lasting responses and improved clinical outcomes in patients who previously had limited treatment options.
Unprecedented Clinical Responses in Heavily Pretreated Patients
The Phase I clinical trial, whose results were recently published in the prestigious journal Blood, enrolled ten patients with relapsed or refractory classical Hodgkin lymphoma or CD30+ T-cell lymphoma. Dr. Javier Briones, Head of the Haematological Oncology and Transplant Research Group at IR Sant Pau and Head of the Haematology Department at Sant Pau Hospital, led the study.
"The most remarkable aspect is the 100% overall response rate, which is extremely rare in patients who have undergone multiple lines of treatment," Dr. Briones explained. "Additionally, 50% of patients achieved complete remission, meaning the disease was undetectable in imaging studies and clinical analyses."
The durability of response has been particularly impressive, with 60% of patients who achieved complete remission remaining disease-free after a median follow-up of 34 months. This sustained efficacy addresses one of the major limitations of previous CAR-T approaches for CD30+ lymphomas, which often suffered from poor persistence of the modified cells and high relapse rates.
Enhanced Safety Profile and Cellular Persistence
From a safety perspective, HSP-CAR30 demonstrated a favorable profile with no dose-limiting toxicities. Six patients experienced only Grade 1 cytokine release syndrome (CRS), and notably, none developed neurotoxicity—a significant concern with many CAR-T therapies. The mild and manageable adverse effects further support the clinical viability of this approach.
One of the study's most significant findings was the remarkable persistence of CAR30+ cells, which remained detectable in 60% of evaluable patients one year after infusion. During peak expansion, researchers observed a predominance of central memory T cells (TCM) and stem-like memory T cells (TSCM-LIKE), cell types associated with treatment efficacy and durability.
Dr. Ana Caballero, Consultant Haematologist and co-investigator of the trial, emphasized the importance of these findings: "These results suggest that selecting the CD30 epitope and preserving less differentiated T cells ex vivo may enhance CAR-T therapy efficacy in patients with refractory Hodgkin lymphoma. If we can demonstrate in larger studies that this strategy works long-term, we could be looking at a paradigm shift in the treatment of refractory CD30+ lymphomas."
Technological Innovations Driving Success
HSP-CAR30 represents a significant advancement over previous CAR-T approaches for CD30+ lymphomas. The therapy is designed to target a more stable region of the CD30 protein, preventing tumors from evading attack by shedding CD30 fragments into the bloodstream—a common mechanism of resistance.
The manufacturing process has been refined to enhance the quality and persistence of the modified T cells. An innovative strategy combining interleukin-21 (IL-21) with IL-7 and IL-15 has been implemented to promote the expansion of long-lived memory T cells, ensuring both immediate efficacy and lasting protection against disease recurrence.
"The goal of this optimisation is to ensure that CAR-T cells are not only effective at the outset but also remain active in the body for a much longer period," explained Dr. Laura Escribà, senior researcher and Director of Quality Control for CART30 Production. "We want the patient's immune system to retain a group of defence cells ready to act should the cancer attempt to return."
Expanding Clinical Investigation
HSP-CAR30 is the first European CAR-T30 study to successfully complete its initial phase. The promising results from the Phase I trial have led to an expanded Phase II investigation, which has already treated 32 additional patients.
Preliminary findings from the Phase II trial were presented at the 2024 annual meeting of the American Society of Hematology (ASH). According to Dr. Caballero, over 55% of patients in Phase II achieved complete remission, further validating the therapy's potential.
The study is registered on ClinicalTrials.gov (NCT04653649) and continues to evaluate the efficacy of HSP-CAR30 in a larger cohort. If these results are confirmed in subsequent studies, this innovative therapy could represent a major advancement in treating CD30+ lymphomas, which have historically posed significant therapeutic challenges.
Multi-Institutional Support
The development of HSP-CAR30 has been made possible through substantial support from multiple organizations. The Josep Carreras Leukaemia Foundation and Research Institute have played a crucial role, contributing over two million euros to help launch the trial and acquiring essential equipment for cell production.
Additional support has come from La Marató de TV3, the Carlos III Health Institute, the 'La Caixa' Foundation, the Agency for the Management of University and Research Grants, and the Network of Advanced Therapies. The Blood and Tissue Bank has also provided important backing for the study.
This collaborative approach has enabled researchers to overcome significant technical and financial challenges in developing this promising new therapy, potentially offering new hope to patients with limited treatment options.
