Novel Car-Topy Achieves Positive Results in a High Propertion of Patients with a Refractory Type of Lymphoma

Researchers from the Sant Pau Research Institute (IR Sant Pau), in Collaboration with Sant Pau Hospital and the Josep Carreras Leukemia Research Institute, have developed anovative car-T cell Therapy Targeting The CD30 Protein (HSP-Car30), Which Has Shown High Effficacy in Patients with refractory CD30+ lymphoma.

The Phase I Trial Clinical, Whinse Results have been published In the Journal BloodReveals That This New Car-T30 Therapy Promotes The Expansion of Memory T Cells, Leading to Long-Lasting Responses and Improved Clinical Outcomes in Treated Patients.

Hodgkin lymphoma and other CD30⁺ Lymphomas have posed a significant challenge to the medical community, particularly in refractory or relapsed cases where conventional treatments have so fari bordin effficacy.

RECENTLY, CAR-T CELL THERAPIES Have emerged as promising alternative for treating hematological malignances, Achieving very positive results in b-cell leukemias and lymphomas. However, Their Application to CD30⁺ Lymphomas has Been Limited Due to the Lack of Persistence of Modified Cells and the High Relation Rate Patients. Addihthally, The Exceptionally Low Number of Clinical Trials in This Context has Hindered the Development of New Solutions.

THANKS TO ADVANCE IN GENETIC ENGINEERING AND BIOTECHNOLOGY, THE TEAM AT SANT PAU HAS OVERCOME CHALLENGES BY DEVELOPING HSP-Car30, AN OPTIMIZED VERSION OF CAR-T THERAPY INCORPORATING NEW STRATEGIES TO IMPROVALITY AND DUBLILITY OF THERAPUTIC CELLS. This Breakthrough Representatives A Milestone in the Fight Against these Types of Cancer and Opens New Possibilities for Patients Who Previously Had Very Few Treatment Options.

The Phase I Trial Involved 10 Patients with Related or Refractory Classical Hodgkin Lymphoma or CD30⁺ T-Cell Lymphoma, Yielding Highly Positive Results.

Dr. Javier Briones, Head of the Hematological Oncology and Transplant Research Group at IR Sant Pau and Head of the Hematology Department at Sant Pau Hospital, Led the Study and States That It “Most Remarkable aspect is the 100% Overall Response Rate, Which is extremly rare in patients who have Undergone Multiple Lines of Treatment. AddiTionally, 50% of Patients Achieved Complete Remission, Meaning The Disease Was Undetectable in Imaging Studies and Clinical Analyses.

Regarding the durability of the Response, 60% of Patients Who Achieved A Complete Response Remained In remunion with no signs of relapse after median follow-up of 34 months. “This is crucial,” Explains Dr. Briones, “BECAUSE it indicates that the persistence of Car-T Cells in the Body has a Real and Lasting Impact On The Disease, Which is Precisély What We Aim for This Type of Therapy.”

From the Safety Perspective, The Treatment Exhibited A Favorable Profile, with no dose-limiting toxicities detected. Six Patients Experienced Grid 1 Cytokine Release Syndrome (CRS), and None Developed Neurotoxycy. The Observed Adverse Effects Were Mild and Manageable, Reinforcing the Feasability of This therapy for Clinical Application.

One of the Most Significant Findings of the Study was the High in Vivo Persistence of Car30⁺ Cells, Which Remained Detectable in 60% of Evaluable Patients One Year After Infusion. FURTHERMORE, During the Peak Expansion of T Cells, There was the predominance of Central Memory T Cells (TCM) and Stem-Like Memory T Cells (TSCM-Like), Which Are Associated with Treatment Effficacy and durability.

Promising Future for Patients with Refractory Lymphoma

“These Results Suggest That Selecting The CD30 Epitope and Preserving Less Differentiated T Cells Ex vivo May Enhance Car-T therapy EFFICACY with Refractory Hodgkin Lymphoma,” States Dr. Ana Caballero, Consultant Hematologist and Co-Investigator of the Trial.

She HighLights The Significance Of This Discovery: “If we can demonstrate in Larger Studies That This Strategy Works Long-Term, We Could Be Looking at Paradigm Shift in the Treatment of Refractory CD30⁺ Lymphomas. This will be BRING HOPE TO MANY PATIES WITH VEY LIMITED THERAPEUTIC OPTIONS. “

The Study is registered on clinicaltrials.gov (NCT04653649) and is currently in an extended analysis phase to Evaluate the effectiveness of hsp-car30 in a large cohort. IF these results are confirmed in subsequent studies, this Innovative therapy could representing Major Advancement in Combating This Disease.

HSP-Car30: Pioneering Study in Europe

HSP-Car30 Is the First European Car-T30 Study to Successfully Complete Its Initial Phase. The Results of the Phase I Trial, Now Published in Bloodand preliminary findings from the Phase II Trial Were Gifted at the 2024 Annual Meeting of the American Society of Hematology (Ash), One of the Most Significant Scientific Gatherings Held at the End of Last Year.

TO DATE, 32 PAIENTS HAVE BEEN TREATED with HSP-Car30 In The Phase II Trial, with an addititional 10 Patients Included to Strengthen the Roblestness of the Findings. According to Dr. Caballero, this expansion Will provides more solid foundation for the future develope of this therapy.

“The Fact That Over 55% of Patients Achieved Complete Remission in Phase II Endrages Us to Move Forward. These Results are Highly Promising for A Population With Limited Treatment Options,” She Staed.

The New Approach to Car-T Therapy for CD30⁺ lymphoma

CAR-T CELLS ACT A A Specialized Imamune Force. These Cells are extraced from the Patient and Modified in the Laboratory to Recognize and Attack Specific Cancer Cells. In this case, HSP-Car30 is designated to target the cd30 protein, Which is present on the tumor Cells of Hodgkin Lymphoma and one’s other CD30⁺ Lymphomas But Rarely Expressed on Healthy Cells.

Previous Car-t Therapies Faced Challenges Where, Railing Their Initial Effectiveness, Many of These Cells Became Exhausted too Quickly or Lost Their Ability to Fight Cancer Long-Term. To Overcome This, Researchers Optimized HSP-Car30 to Target A More Stable Region of the CD30 Protein, Preventing The Tumor from Evading Attack by Shedding CD30 Fragments Into the Bloodstream.

Addihthally, The Manufacturing Process has been refined to Enhance the Quality and Persistence of Modified T Cells. An Innovative Strategy Combining Interleukin-21 (IL-21) with IL-7 and Il-15 has ben implemented to promote the expansion of long-lived memory t cells. This teach that therapy is not only effective in the short but also offsters a greater likeliod of lasting protection against the disease.

Dr. Laura Escriba, Senior Researcher and Director of Quality Control for Cart30 Production, Explains, “The Goal of This Optimization is to Ensure That Car-T Cells Are Not Only Effective at the Outset But Rue Remain Active in the Body For Much Period. To Retain a group of Defense Cells Ready to Act Should The Cancer Attempt To Return. “