Australian researchers have developed a new targeted therapy ― a type of immunotherapy called an antibody-drug conjugate ― to treat one of the deadliest blood cancers in children, Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like ALL).
In a study led by Children’s Cancer Institute and published this month in the high-impact international journal Leukemia, the researchers tested the new therapy in living laboratory models of Ph-like-ALL, demonstrating that it selectively binds to and destroys leukaemia cells, leading to extended survival.
‘This study introduces a new targeted treatment approach for a high‑risk form of childhood leukaemia that currently has very limited treatment options,’ said Dr Sara Mohamed, Research Officer in the Leukaemia Biology Program at Children’s Cancer Institute, and lead author on the published study. ‘In our preclinical models, we saw strong anti‑leukaemia activity ― results which we believe provide a firm foundation for future clinical development.’
The immunotherapy featured in the study combines an antibody that specifically recognises Ph-like ALL cells with a drug designed to destroy these cells, together acting as a highly precise, targeted system. The therapy has also been designed to avoid the major clinical problem of treatment resistance ― when cancer cells evade treatment by losing the molecules targeted by the therapy.
‘Our antibody-drug conjugate selectively targets a protein called CRLF2, which often occurs at high levels in Ph-like ALL, and is known to be linked to disease progression and relapse,’ explained Professor Richard Lock, Head of the Cancer Biology Theme at Children’s Cancer Institute, and senior author on the study. ‘This is in contrast to currently available immunotherapies which target other molecules, primarily CD-19 or 22, which cancer cells can readily lose, allowing them to escape being killed.’
‘By targeting CRLF2, the new therapy may improve treatment precision while at the same time reducing the likelihood of resistance, leading to longer‑lasting control of disease,’ said Dr Narges Bayat, a Senior Research Officer at Children’s Cancer Institute, and co-senior author on the study.
Having provided proof-of-concept of the efficacy of the novel therapy, the team is hopeful their research paves the way to the clinical development of a new and much-needed treatment option for children with high‑risk leukaemia.
This research was funded by the National Health and Medical Research Council, and involved collaboration with the Garvan Institute of Medical Research, and Jena University Hospital (Germany).
Read the research paper here: A novel CRLF2-targeted antibody-drug conjugate exhibits potent anti-leukemic activity against Ph-like acute lymphoblastic leukemia | Leukemia
