A new CAR-T therapy obtains positive results in a high proportion of patients with a refractory type of lymphoma

Researchers from the Sant Pau Research Institute (Ir Sant Pau), in collaboration with the Sant Pau hospital and the Josep Carreras Leukemia Research Institute, have developed innovative CAR-T cell therapy targeting the CD30 protein (HSP-Car30), which has shown high efficiency in patients with CD30 + refractory lymphoma.

A phase I clinical trial, the results of which were published in the journal Bloodreveals that this new CAR-T30 therapy promotes the expansion of T memory T cells, leading to lasting responses and to improve clinical results in treated patients.

Hodgkin’s lymphoma and other CD30⁺ Lymphomas have posed an important challenge for the medical community, in particular in refractory or relapse cases where conventional treatments have so far shown limited efficiency.

Recently, CAR-T cell therapies have become a promising alternative to treat hematological malignant tumors, obtaining very positive results in leukemia and cell cells. However, their application to CD30⁺ Lymphomas have been limited due to the lack of persistence of modified cells and the high relapse rate in patients. In addition, the exceptionally low number of clinical trials in this context has hampered the development of new solutions.

Thanks to the progress of genetic engineering and biotechnology, the Ir Sant Pau team overcome these challenges by developing HSP-Car30, an optimized version of CAR-T therapy incorporating new strategies to improve the functionality and sustainability of therapeutic cells. This breakthrough represents an important step in the fight against these types of cancer and opens up new possibilities for patients who previously had very few treatment options.

Phase I test involved 10 patients with classic Hodgkinian lymphoma in relapse or refractory or CD30⁺ T cell lymphoma, which gives very positive results.

Dr. Javier Briones, head of the hematological research group in oncology and transplantation at Ir Sant Pau and head of the Hospital Department of Sant Pau hospital, directed the study and declares that his “most remarkable aspect is the rate of response to 100% global, which is extremely rare in patients who have undergone several lines of treatment.

Regarding the sustainability of the response, 60% of patients who obtained a complete response remained in remission without a relapse sign after a median follow -up of 34 months. “It’s crucial”, explains Dr. Brones, “because it indicates that the persistence of CAR-T cells in the body has a real and lasting impact on the disease, which is precisely what we are targeting with this type of therapy.”

From a safety point of view, the treatment had a favorable profile, without any toxicity limiting the detected dose. Six patients underwent a grade 1 cytokine liberation syndrome (CRS) and none has developed neurotoxicity. The undesirable effects observed were light and manageable, strengthening the feasibility of this therapy for clinical application.

One of the most important conclusions of the study was the strong in vivo persistence of Car30⁺ Cells, which remained detectable in 60% of patients evaluated one year after infusion. In addition, during the maximum expansion of T cells, there was a predominance of the T cells of central memory (TCM) and T -type T -type cells (TSCM type), which are associated with the effectiveness of treatment and sustainability.

A promising future for patients with refractory lymphoma

“These results suggest that the selection of the CD30 epitope and the preservation of the less differentiated T cells can improve the efficiency of CAR-T therapy in patients with refractory Hodgkinian lymphoma,” said Dr. Ana Caballero, a consultant and co-investigator of the test.

It underlines the importance of this discovery: “If we can demonstrate in more important studies that this strategy works in the long term, we could examine a paradigm change in the treatment of the refractory CD30⁺ lymphomas. This would hope for many patients with very limited therapeutic options. “”

The study is registered on clinicals.gov (NCT04653649) and is currently in an extensive analysis phase to assess the efficiency of HSP-Car30 in a larger cohort. If these results are confirmed in subsequent studies, this innovative therapy could represent major progress in the fight against this disease.

HSP-Car30: A pioneer 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 the preliminary results of the phase II test were presented at the annual meeting of the American Society of Hematology (ASH), one of the most important scientific gatherings organized at the end of last year.

To date, 32 patients have been treated with HSP-Car30 in phase II trial, with 10 additional patients included to strengthen the robustness of the results. According to Dr. Caballero, this expansion will provide a more solid base for the future development of this therapy.

“The fact that more than 55% of patients have obtained complete remission in phase II encourages us to move forward. These results are very promising for a population with limited processing options,” she said.

A new approach to CAR-T therapy for CD30⁺ lymphoma

CAR-T cells act as a specialized immune force. These cells are 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 on the tumor cells of Hodgkin’s lymphoma and other CD30⁺ lymphomas but rarely expressed on healthy cells.

Previous therapies of CAR-T were faced with challenges where, despite their initial efficiency, many of these cells have become exhausted too quickly or have lost their ability to combat long-term cancer. To overcome this, the researchers optimized HSP-Car30 to target a more stable region of the CD30 protein, preventing the tumor from escaping the attack by eliminating CD30 fragments in the blood circulation.

In addition, the manufacturing process has been refined to improve the quality and persistence of 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 T memory. This ensures that therapy is not only effective in the short term, but also offers a greater probability of sustainable protection against the disease.

Dr. Laura Escripà, principal researcher and director of quality control of Cart30 production, explains: “The purpose of this optimization is to ensure that CAR-T cells are not only effective at the start, but also remain active in the body for a much longer period. We want the patient’s immune system to keep a group of defense cells ready to act if cancer tries to come back.”