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DBM Research Prize Winner 2023 / 2024
Congratulations to Dr. Simon Garaudé and Dr. Romina Marone, the recipients of this year’s DBM Research Prize for their work on gentler cell therapies for blood cancer. Published in Nature, this groundbreaking study introduces a novel method to selectively eradicate hematological cancers while preserving healthy hematopoiesis – a finding with broad therapeutic potential.
Leukemia treatment traditionally requires intensive chemotherapy to eliminate both the patient’s blood cells and hematopoietic stem cells, followed by the risky and complex transplantation of donor stem cells (HSCT). However, its effectiveness is limited by the need for broad-spectrum chemotherapies for the pre-conditioning of patients and the challenges of targeting malignant cells post-transplant. Antigen-specific cell-depleting therapies, like antibody-drug conjugates (ADCs), have shown promise in enhancing HSCT, particularly for B cell malignancies, but finding antigens with profiles as favorable as CD19 is challenging. The new method, led by Professor Lukas Jeker, simplifies this process by using a targeted approach to remove all blood cells while introducing new, healthy stem cells.
As a target, Simon and Romina chose CD45, a marker that is highly expressed on blood cancers but also on healthy blood cells. This profile until now has prevented effective targeting of CD45 for therapeutic purposes. In a notable advance, Simon, Romina and their co-authors developed a novel HSCT approach by editing transplanted HSPCs with base editor mRNAs and single guide RNAs in order to engineer CD45 so that the surface protein evades recognition by an anti-CD45 antibody. They could show that acute myeloid leukemia (AML) cells can be eliminated using a CD45-targeting ADC derived from the tested antibody while transplanted engineered HSCs were shielded from the CD45-directed therapy, therefore preserving healthy hematopoiesis. This strategy not only holds promise for improving treatments for hematological cancers but also offers potential benefits for severe autoimmune diseases and possibly also HIV infection.
The team's innovative approach represents a significant advancement in cancer treatment, aiming to specifically target malignant cells while preserving normal blood cells. This breakthrough promises to transform the treatment landscape for patients with hematological malignancies, providing new hope for recovery with minimal collateral damage.
Congratulations to the team for their remarkable achievement and for pushing the boundaries of cancer research!