Swiss researchers have unveiled a “gentler” approach to haematopoietic stem cell transplants, aimed at reducing side effects and complications.
The researchers from the University of Basel say they have developed a method that allows donor stem cells to be administered while chemotherapy is destroying the diseased blood system.
The technique involves using an antibody-drug conjugate to destroy the diseased cells while modifying the donor’s stem cells to ensure the antibody treatment avoids them.
Study leader Professor Lukas Jeker said: “We needed a surface molecule that appeared with approximately the same frequency on all blood cells if possible, including the leukaemia cells, but that wasn’t present on other cells in the body.”
Their chosen surface molecule is CD45, which is expressed on normal blood stem cells and most blood cancer cells. The team developed a method to modify CD45, rendering it undetectable by the antibody-drug conjugate but maintaining its ability to function normally.
This means that modified donor stem cells could be administered to recipients while their diseased blood system is depleted with the antibody-drug conjugate.
The proposals have been reported in Nature and have been funded with a grant of 2.4 million euros from the European Research Council.
The researchers believe it is a significant step towards a “programmable” blood system, and hope to begin clinical trials within a few years.
Romina Matter-Marone, joint first author of the study, said: “The new approach could pave the way for new treatment options for patients whose state of health is incompatible with the chemotherapy needed for stem cell transplantation.”
Source:
Garaudé S, Marone R, Lepore R, Devaux A, Beerlage A, Seyres D, Dell' Aglio A, Juskevicius D, Zuin J, Burgold T, Wang S, Katta V, Manquen G, Li Y, Larrue C, Camus A, Durzynska I, Wellinger LC, Kirby I, Van Berkel PH, Kunz C, Tamburini J, Bertoni F, Widmer CC, Tsai SQ, Simonetta F, Urlinger S, Jeker LT. (2024) “Selective haematological cancer eradication with preserved haematopoiesis.” Nature, 22 May 2024, doi: 10.1038/s41586-024-07456-3.
Link: https://www.nature.com/articles/s41586-024-07456-3
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