In a ‘proof-of-concept’ study, scientists have developed a new form of T cell therapy that could effectively target a specific gene mutation to treat acute myeloid leukaemia (AML).
There is currently no approved immunotherapy for AML except for stem cell transplantation. What’s more, the effectiveness of tyrosine kinase inhibitors towards leukaemias with mutations is variable. So a team led by Professor Johanna Olweus of the University of Oslo in Norway, investigated a new approach.
The authors write: “Acute myeloid leukaemia, the most frequent leukaemia in adults, is driven by recurrent somatically acquired genetic lesions in a restricted number of genes.”
The Norwegian scientists worked with colleagues at Karolinska Institutet in Sweden to identify a T-cell receptor that recognises a specific mutation in the FLT3 gene, which is shared between a subgroup of patients.
When they engineered T cells to produce this T-cell receptor, it enabled them to identify and destroy leukaemia cells with the same mutation – called FLT3D835Y. This was confirmed in tests on cells, and in animal models of AML.
Details were published in Nature Cancer last week.
“Thus, T cells targeting a single shared mutation can provide efficient immunotherapy toward selective elimination of clonally involved primary acute myeloid leukaemia,” they write.
Professor Olweus commented: “Almost all mutations are unique to the individual cancer tumour and patient, and targeted treatment must therefore be tailored to each individual patient.
“We also know that many mutations exist only in some cancer cells, which allows other cancer cells to escape treatment. In addition, only a few mutations are recognised by the immune cells.
“This provides hope that we can develop a new and effective treatment for acute myeloid leukaemia, with likely relevance also for other cancer types.”
Giannakopoulou E, Lehander M, Virding Culleton S, Yang W, Li Y, Karpanen T, Yoshizato T, Rustad EH, Nielsen MM, Bollineni RC, Tran TT, Delic-Sarac M, Gjerdingen TJ, Douvlataniotis K, Laos M, Ali M, Hillen A, Mazzi S, Chin DWL, Mehta A, Holm JS, Bentzen AK, Bill M, Griffioen M, Gedde-Dahl T, Lehmann S, Jacobsen SEW, Woll PS, Olweus J. (2023) “A T-cell receptor targeting a recurrent driver mutation in FLT3 mediates elimination of primary human acute myeloid leukemia in vivo.” Nature Cancer, doi: 10.1038/s43018-023-00642-8
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