2:56 PM
 | 
Dec 05, 2018
 |  BC Extra  |  Tools & Techniques

Proteogenomic screen identifies non-mutated tumor-specific antigens

A University of Montreal team has developed a proteogenomic screen that identifies mutated and non-mutated tumor-specific TCR antigens, including those arising from normally non-coding nucleotide sequences. The technique could help develop T cell immunotherapies targeting non-mutated, but aberantly expressed, tumor-specific antigens, which could be shared between cancer patients.

In a Science Translational Medicine paper, the researchers described the screen, a combination of transcriptomic and proteomic analyses.

The team first developed a database that combines two data sets of cancer peptides. The first set comprises all proteins computationally translated from tumor cell RNA sequences. The second set was created by translating peptides from RNA sequences in all genomic regions in the cancer cells after removing 33-nucleotide sequences present in healthy cell transcriptomes. By doing so, the team expanded the peptide pool beyond exonic reading frames to non-coding genomic regions.

The method then cross-references the nucleotide sequences of MHC-displayed peptides from tumor cells, including transcription levels, with the cancer database to identify candidate tumor-specific antigens.

Using the screen, the scientists identified six neoantigens and 11 non-mutated tumor-specific antigens from mouse colorectal cancer and lymphoma cell lines. They also applied the method to tumor samples from four B cell acute lymphoblastic leukemia (ALL) patients and three lung cancer patients, and identified 20 non-mutated tumor-specific antigens. Author Claude Perreault, professor of medicine at University of Montreal, said that the antigens "are shared by many/most patients with a given tumor type."

Vaccination with dendritic cells displaying five of the identified mouse lymphoma non-mutated antigens prolonged survival in a mouse model of lymphoma. Three of the vaccinations also enabled mice to survive a second challenge with lymphoma cells.

Perreault said his team plans to use the screen to identify shared tumor-specific antigens for different cancer indications. He told BioCentury he envisions the method could be used to develop cancer vaccines or TCR-based immunotherapies.

Perreault added that his team has partnered with AbbVie Inc. (NYSE:ABBV) to discover tumor-specific antigens in leukemia.

User Sign in

Trial Subscription

Get a 4-week free trial subscription to BioCentury Extra

Article Purchase

Purchase this article for limited one-time distribution and website posting

$750 USD