Unmutated Tumor Antigens: New Immunotherapy Targets

The team headed by Claude Perreault, Director of IRIC's Immunobiology Research Unit and and Professor at the Faculty of Medicine at Université de Montréal, has identified novel tumor antigens that could lead to the development of vaccines for the treatment of two cancers: melanoma and non-small cell lung cancer.

To achieve this, the team led by PhD student Anca Apavaloaei has adopted an unbiased approach that examines all genetic material, including DNA described as "junk" because it is not coding for any known protein. The work, the fruit of collaborations with the Epitopea company, McGill University, the University of Liège and the University of Lausanne, has been published in the journal Nature Cancer.

Defying predictions

Anca Apavaloaei and Claude Perreault

Anca Apavaloaei and Claude Perreault

Credit: Courtesy

Melanoma and non-small cell lung cancer are two cancers with many mutations. It has long been predicted that immunotherapies could target them by recognizing fragments proteins, called tumor antigens, containing mutations on the surface on cancer cells.

With their unbiased approach based on mass spectrometry, the team found instead that these mutated tumor antigens accounted for only 1% of all tumor antigens. Among the 584 unmutated tumor antigens discovered, 220 are particularly interesting because they are present exclusively in cancer cells.

Abundant, exploitable targets

These non-mutated antigens are present in the various tumor samples tested and are immunogenic, i.e. they can initiate an immune system response. These two properties confirm their clinical potential as targets for immunotherapy in melanoma and non-small cell lung cancer.

"The unmutated tumor antigens described in this study will undergo extensive validation before being tested in clinical trials," notes Anca Apavaloaei, now a postdoctoral fellow at Weill Cornell Medicine. "We hope that in the near future, vaccines targeting these antigens will significantly improve treatments for melanoma and non-small cell lung cancer."

About this study

The article "Tumor antigens preferentially derive from unmutated genomic sequences in melanoma and non-small cell lung cancer" by Claude Perreault and his colleagues was published in the journal Nature Cancer on May 22.

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