Researchers at the Sant Pau Research Institute (IR Sant Pau), in collaboration with the Hospital de Sant Pau and the Josep Carreras Leukaemia Research Institute, have developed an innovative CAR-T cell therapy targeting the CD30 protein (HSP-CAR30), which has shown high efficacy in patients with refractory CD30+ lymphoma. In a phase I clinical trial, the results of which have been published in the prestigious journal Blood, this new CART30 has been shown to promote the expansion of memory T cells, leading to durable responses and improved clinical outcomes in treated patients.
Hodgkin lymphoma and other CD30+ lymphomas have posed a major challenge to the medical community, especially in relapsed or refractory cases where conventional treatments have so far shown limited effectiveness. Recently, CAR-T cell therapies have emerged as a promising alternative for the treatment of hematological malignancies, achieving highly positive results in leukemias and B-cell lymphomas. However, their application in CD30+ lymphomas has been limited due to the lack of persistence of the modified cells and the rapid relapse of patients. It is also worth noting the exceptionally low number of clinical trials in this area, which has hampered the development of new solutions.
Thanks to advances in genetic engineering and biotechnology, the IR Sant Pau team has managed to overcome these limitations with the creation of HSP-CAR30, an optimized version of CAR-T therapy that incorporates new strategies to improve the functionality and durability of therapeutic cells. This development represents a milestone in the fight against these types of cancer and opens new possibilities for patients who previously had very limited options.
The phase I clinical trial included ten patients with relapsed or refractory classical Hodgkin lymphoma or CD30-positive T-cell lymphoma, with very positive results. According to Dr. Javier Briones, director of the Hematologic Oncology and Transplant Research Group at IR Sant Pau and head of the Hematology Department at Hospital de Sant Pau, and principal investigator of the study, “The most surprising finding of this study is that the overall response rate was 100%, something very uncommon in patients who have gone through multiple lines of treatment. Moreover, 50% of patients achieved complete remission, meaning the disease completely disappeared in imaging studies and clinical tests.”
Regarding the durability of the response, 60% of the patients who achieved a complete response remained in remission without signs of relapse after a median follow-up of thirty-four months. “This is crucial,” explains Dr. Briones, “because it indicates that the persistence of CAR-T cells in the body has a real and sustained impact on the disease, which is precisely what we look for in this type of therapy.”
From a safety perspective, the treatment showed a favorable profile, with no dose-limiting toxicities detected. Six patients experienced grade 1 cytokine release syndrome (CRS), and none developed neurotoxicity. Thus, the observed adverse effects were mild and manageable, reinforcing the feasibility of this therapy for clinical use.
One of the most notable aspects of the study is the high in vivo persistence of CAR30+ cells, which remained detectable in 60% of evaluable patients one year after infusion. In addition, during the peak of T-cell expansion, a predominance of central memory T cells (TCM) and stem cell-like memory T cells (TSCM-LIKE) was observed—both associated with treatment efficacy and durability.
“These results suggest that selecting the CD30 epitope and preserving less-differentiated T cells ex vivo may improve the efficacy of CAR-T therapy in patients with refractory Hodgkin lymphoma,” states Dr. Ana Caballero, attending physician in the Hematology Department and co-investigator of the trial, who emphasizes the importance of this finding: “If we can demonstrate in larger studies that this strategy works long-term, we may be looking at a paradigm shift in the treatment of refractory CD30+ lymphomas. This would bring hope to many patients who currently have very few viable therapeutic options.”
The study is registered at ClinicalTrials.gov (NCT04653649) and is currently in an expanded analysis phase to evaluate the efficacy of HSP-CAR30 in a larger number of patients. If these results are confirmed in future studies, this innovative therapy could represent a significant breakthrough in the fight against this disease.
The HSP-CAR30 treatment is the first European study of a CAR-T30 therapy to successfully complete its initial phase. The results of the phase I trial, now published in Blood, along with preliminary findings from the phase II trial, were presented at the 2024 Annual Meeting of the American Society of Hematology (ASH), one of the most important events for the scientific community, held late last year.
To date, 32 patients have been treated with HSP-CAR30 in the phase II trial, and the study has been expanded to include an additional 10 patients. According to Dr. Caballero, this expansion will strengthen the robustness of the results and establish a more solid foundation for the future development of this treatment. “The fact that over 55% of patients have achieved complete remission in phase II encourages us to move forward. These results are very hopeful for a population with limited treatment options,” said the researcher.
CAR-T cells act as a specialized army of the immune system. They are cells extracted from the patient and modified in the laboratory to recognize and attack specific cancer cells. In this case, HSP-CAR30 is designed to target the CD30 protein, which is present in tumor cells in Hodgkin lymphoma and other CD30+ lymphomas, and rarely expressed in healthy cells.
The challenge with previous CAR-T therapies was that, despite their initial effectiveness, many of these cells became exhausted too quickly or lost their ability to attack cancer over the long term. To overcome this barrier, researchers optimized the structure of HSP-CAR30 by directing it to a more stable region of the CD30 protein, preventing the tumor from evading the CAR-T cells by releasing CD30 fragments into the bloodstream.
Additionally, the manufacturing process has been refined to improve 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, promoting the expansion of T cells with long-term memory characteristics. This means that the treatment is not only effective in the short term but also offers a higher likelihood of lasting protection against the disease.
Dr. Laura Escribà, senior researcher and director of CART30 Production Quality Control, explains: “The goal of this optimization is to ensure that CAR-T cells are not only effective initially but remain active in the body for much longer. We want the patient’s immune system to retain a pool of defense cells ready to act in case the cancer tries to return.”
Several organizations and foundations have supported the Sant Pau project. The Josep Carreras Foundation against Leukaemia and the Josep Carreras Leukaemia Research Institute played a key role in the project by acquiring essential equipment and providing funding for the production of therapies for the first ten patients. In this regard, the Josep Carreras Institute acquired two new cell production units that have been installed at Sant Pau. For the purchase of the first one, the Josep Carreras Foundation launched a fundraising campaign in 2018 titled “The Unstoppable Cell Factory.” The Josep Carreras Foundation has contributed over two million euros to support the launch of this trial.
This study was also made possible thanks to the support of other institutions and funding bodies. In particular, it has received backing from La Marató de TV3 (Exp. 20130710), the Carlos III Health Institute (ISCIII FIS PI15/1383 and PI18/01023; European Union), the “La Caixa” Foundation, the Agency for the Management of University and Research Grants (AGAUR, SGR2021/1139), and the Network for Advanced Therapies (RICORS, ISCIII; RD21/0017/0011; Next Generation, European Union). The study has also received support from the Blood and Tissue Bank (BST).
Caballero AC, Ujaldón-Miró C, Pujol-Fernández P, Montserrat-Torres R, Guardiola-Perello M, Escudero-López E, Garcia-Cadenas I, Esquirol A, Martino R, Jara-Bustamante P, Ezquerra P, Soria JM, Iranzo E, Moreno-Martinez M-E, Riba M, Sierra J, Alvarez-Fernández C, Escribà-Garcia L, Briones J. HSP-CAR30 with a high proportion of less-differentiated T cells promotes durable responses in refractory CD30+ lymphoma. Blood 2025;145:1788–801. https://doi.org/10.1182/blood.2024026758
