Researchers have used genomic sequencing to analyse patterns of neoantigens in multiple myeloma patients, with a view to developing improved immunotherapy.
Neoantigens are by-products from gene mutations in tumours that have not yet been recognised by the immune system.
Dr Samir Parekh, of the Icahn School of Medicine at Mount Sinai, New York, USA, and colleagues analysed next-generation sequencing information to look for neoantigens in myeloma cells from 184 patients. They then looked at which neoantigen-specific immune cells are triggered by immunotherapy. They hope their findings will help tailor specific immunotherapy for this condition.
Details appeared in the journal Clinical Cancer Research. The team say this is the first study to show which neoantigens trigger the immune system to recognise and kill cancer cells in multiple myeloma.
“The results provide the foundation for using neoantigen-targeting strategies such as cancer vaccines in future trials for multiple myeloma patients,” they write.
Patients with relapsed disease tended to have more neoantigens than newly-diagnosed patients, which “may indicate potential for greater immune responses to immunotherapy in these patients,” the researchers say.
Dr Parekh said: “Tumour neoantigens represent excellent targets for immunotherapy, due to their specific expression in cancer tissue. Until now, there has been no direct evidence that DNA mutations induce neoantigen-specific T-cell responses following immunotherapy in multiple myeloma.”
Co-author Dr Nina Bhardwaj is taking the work further in a clinical trial of the safety and effectiveness of a personalised neoantigen vaccine for multiple myeloma, and possibly other cancers.
Source: Perumal D, Imai N, Laganà A, Finnigan J, Melnekoff D, Leshchenko VV, Solovyov A, Madduri D, Chari A, Cho HJ, Dudley JT, Brody JD, Jagannath S, Greenbaum B, Gnjatic S, Bhardwaj N, Parekh S. (2019) “Mutation-derived Neoantigen-specific T-cell Responses in Multiple Myeloma”, Clinical Cancer Research, doi: 10.1158/1078-0432.CCR-19-2309
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