Blood cancer – Prof. Carsten Riether (UNIBE) and Dr. Marc Wehrli (INSELSPITAL)

Enhancing CAR-T Cell Therapy for Refractory Multiple Myeloma

In December 2024, this “allocated fund”, amounting to CHF 100’000, was granted to Prof. Carsten Riether and Dr. Marc Wehrli for one year.

Chimeric antigen receptor (CAR) T cells represent a significant advancement in cancer immunotherapy, especially for blood cancers. This treatment involves genetically modifying a patient’s T cells to express engineered receptors that more effectively eliminate cancer cells. Recent advances focus on enhancing the effectiveness of CAR-T cell therapy for patients with relapsed or refractory multiple myeloma (MM).

MM is a type of blood cancer that originates from malignant plasma cells in the bone marrow. Despite recent advancements in treatments, MM remains a challenging disease due to its recurrent nature. B-cell maturation antigen (BCMA) targeting CAR-T cell therapy has demonstrated effectiveness, but its benefits are often short-lived.

This research seeks to identify specific surface proteins that could enhance the performance of BCMA CAR T cells. We will be conducting an analysis of blood samples from 20 patients. This group includes 10 patients who are either experiencing progressive or stable disease following CAR-T therapy and 10 patients who have achieved a complete response. Blood samples will be collected at various intervals. Our aim is to isolate anti-BCMA CAR-T cells from these samples to perform a CRISPR screening. This screening will target surface proteins that have been identified through advanced techniques in single-cell RNA sequencing. Ultimately, this study aims to identify surface proteins that enhance the persistence of CAR-T cells in multiple myeloma. This identification will lay the foundation for the next generation of BCMA CAR-T cell therapies, which could significantly improve patient outcomes.