Barcelona, April 29, 2025 – In a pioneering leap forward in hematologic oncology, researchers at the Sant Pau Research Institute (IR Sant Pau), synergizing efforts with the Hospital de Sant Pau and the Josep Carreras Leukaemia Research Institute, have unveiled a novel CAR-T cell therapy targeting the CD30 antigen, designated as HSP-CAR30. This innovative cellular immunotherapy has demonstrated exceptional potency against refractory CD30-positive lymphomas in a recently completed Phase I clinical trial, the outcomes of which were published in the prestigious journal Blood. Distinctively, HSP-CAR30 enhances memory T cell expansion, a critical feature attributed to durable therapeutic remissions and improved patient prognoses.
Classical Hodgkin lymphoma and other CD30-expressing lymphomas have long been entrenched as therapeutic challenges, particularly when standard regimens fall short in relapsed or refractory presentations. While CAR-T therapies have revolutionized treatment paradigms for B-cell malignancies by reprogramming immune cells to eradicate cancer, their deployment in CD30+ lymphoma patients has encountered obstacles, notably the limited persistence of infused CAR-T cells and rapid disease recurrence. Until now, the field has been constrained by a paucity of rigorous clinical investigations dedicated specifically to these lymphomas, stalling progress in their treatment.
The scientific team at IR Sant Pau employed advanced genetic engineering techniques to overcome these hurdles, culminating in the creation of HSP-CAR30—an optimized CAR-T construct designed to enhance both the longevity and antitumor activity of therapeutic lymphocytes. This refinement includes targeting a more stable epitope on the CD30 protein to prevent tumor immune evasion, a strategy informed by detailed molecular analyses revealing the structural vulnerabilities exploited during earlier therapy failures. This breakthrough holds transformative potential for patient populations previously deprived of effective options.
The Phase I trial enrolled a cohort of ten patients contending with relapsed or refractory classical Hodgkin lymphoma or CD30-positive T-cell lymphoma. Astonishingly, the overall response rate reached 100%, a stark contrast to historical outcomes in heavily pretreated cohorts. Notably, half of the participants achieved complete remission, verified through comprehensive imaging and exhaustive clinical evaluations. According to Dr. Javier Briones, lead investigator and director of Hematologic Oncology at IR Sant Pau, this unprecedented efficacy underscores the potent immune-mediated tumor suppression achievable with HSP-CAR30.
Beyond immediate efficacy, the trial highlighted the remarkable durability of responses, with 60% of patients maintaining remission at a median 34-month follow-up. This sustained disease control aligns with the therapy’s ability to establish long-lived memory T cells in vivo, specifically central memory (TCM) and stem cell-like memory (TSCM-like) subsets, which are known to underpin persistent immunosurveillance. Persistent CAR30+ cells were detectable in a majority of evaluable subjects even one year after infusion, marking a significant advancement over prior CAR-T constructs that succumbed prematurely to cellular exhaustion.
Safety evaluations revealed an encouraging toxicity profile. Treated patients predominantly experienced mild, grade 1 cytokine release syndrome (CRS), and crucially, no instances of neurotoxicity were observed. The absence of dose-limiting toxicities signals that HSP-CAR30 can be safely administered, expanding its therapeutic scope. This safety finding is pivotal for clinical translation, particularly given the fragile condition of patients battling relapsed lymphoma.
Central to the therapy’s efficacy is an innovative manufacturing process that integrates interleukins IL-7, IL-15, and IL-21 during ex vivo T-cell expansion. This cytokine cocktail preferentially promotes the generation of less differentiated memory T cells, conferring enhanced proliferative capacity and longevity upon reinfusion. By fostering a reservoir of potent, self-renewing T lymphocytes, HSP-CAR30 ensures sustained antitumor activity and mitigates premature immunologic attrition that has plagued previous CAR-T approaches.
This strategy coincides with deliberate targeting of a stable, non-shedding CD30 epitope, circumventing a key immune evasion mechanism employed by tumors. Earlier CAR-T therapies inadvertently targeted extracellular domains prone to fragment release, blunting immune recognition and facilitating relapse. The precise epitope selection in HSP-CAR30, backed by structural biology insights, represents an intelligent design shift that effectively barricades the therapeutic cells against tumor escape.
As the investigation progresses, Phase II data have already begun to illuminate the therapeutic horizon. Thirty-two patients have been treated with HSP-CAR30, with an expanded cohort adding ten more subjects to solidify findings. Preliminary analyses indicate that over 55% of these patients achieve complete remission, corroborating Phase I results and reinforcing confidence in this approach. The trial’s expansion aims to validate these promising outcomes within a larger, more diverse patient population.
Experts believe this therapy heralds a paradigm shift in treating refractory CD30+ lymphomas. Dr. Ana Caballero, co-investigator and hematology specialist, asserts that if these findings hold in subsequent larger-scale studies, HSP-CAR30 might establish a new standard of care for patients who have exhausted conventional treatments. The dual capability of potent immediate cytotoxicity combined with prolonged immunological memory offers a durable therapeutic platform.
On the technological front, quality control innovations have been critical. Dr. Laura Escribà, overseeing production quality, highlights the stringent manufacturing protocols that ensure consistency and functionality of the CAR-T cells. The incorporation of advanced cell culture techniques, alongside molecular engineering refinements, enables high-yield production of immunocompetent, long-lived CAR-T cells. These processes underscore the translational viability of HSP-CAR30 as a scalable off-the-shelf treatment for hematological malignancies.
The endeavor’s success owes much to multisectoral support. The Josep Carreras Foundation and Leukaemia Research Institute fortified the project with substantial funding and infrastructure, including the establishment of state-of-the-art cell production units at Sant Pau. Additional backing from institutions such as La Marató de TV3, “La Caixa” Foundation, Carlos III Health Institute, and European Union frameworks was instrumental. These collaborations exemplify how targeted investment in cutting-edge immunotherapy research can accelerate clinical breakthroughs.
In sum, HSP-CAR30 exemplifies the confluence of molecular engineering, immunology, and clinical acumen to surmount longstanding challenges in lymphoma therapy. By generating a reservoir of robust, memory-enriched CAR-T cells targeting a strategically chosen antigenic epitope, this therapy offers new hope for patients suffering from refractory CD30+ lymphomas. Future studies will determine if these groundbreaking Phase I and II results translate into long-term remission and survival benefits on a population scale.
Subject of Research: People
Article Title: HSP-CAR30 with a high proportion of less-differentiated T cells promotes durable responses in refractory CD30+ lymphoma
News Publication Date: 29-Apr-2025
Web References:
http://dx.doi.org/10.1182/blood.2024026758
References:
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;145:1788–1801.
Keywords: Cancer treatments, T cell lymphoma, Clinical research, Memory T cells, Clinical trials, Gene therapy, Blood diseases
