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Immunotherapy: exploring the "grey genome" for new therapeutic targets

Institut Curie
06/23/2022
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Institut Curie's technology transfer strategy is once again bearing fruit. Work by Institut Curie team leader Sebastian Amigorena in collaboration with Mnemo Therapeutics, Institut Curie’ spin-off of which he is a co-founder, highlight a novel approach to discovering specific cancer targets for immunotherapy, by probing unknown areas of the genome.
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Published in Cell Reports on June 7, a study conducted by the team of Sebastian Amigorena, CNRS research director and head of the Immune Responses and Cancer team (Institut Curie, Inserm), in collaboration with Mnemo Therapeutics, Institut Curie’ spin-off of which he is a co-founder, has just identified new tumor targets for immunotherapy: peptides derived from transposable elements, also known as "transposons" or "jumping genes," mobile regions of the DNA that move to other areas of the genome.

A novel exploration of the genome to identify new therapeutic targets

The human genome is commonly divided into two broad categories. 4% of the genome codes for proteins and the remaining 96% is made up of non-coding or very little known elements: this is called the "dark genome". The results of this study published in Cell Reports show that new targets specific to tumor cells can be found outside of the 4%, necessitating the expansion of the human genome by including a new area: the "grey genome". This would represent about 45% of the genome and would be composed of transposable elements, non-coding RNAs and some other non-coding transcripts. The researchers revealed increased transcription of these "jumping genes" in certain cancer cells, which suggests that they could code for tumor antigens.

These results, demonstrated in studies of glioblastoma patients, support the development of a novel approach to expand the known range of tumor targets by probing unknown areas of the genome, suggesting its application to a wide range of indications, as explains Sebastian Amigorena:

Known targets are encoded by a very small percentage of the human genome, leaving vast regions rich with potential tumor-specific targets uncharacterized and unexplored. The research in this publication provides foundational evidence that we can probe the grey genome to identify features with promising potential to encode for cancer-specific targets.

A successful technology transfer strategy for Institut Curie

These results were made possible by using a proteogenomic[1] approach combined with the power of Mnemo Therapeutics' EnfiniT discovery engine, a cutting-edge technology tool that identifies novel cancer-specific antigens and enhances immune cell memory and persistence. Mnemo Tx[2], Institut Curie spin-off company co-founded in 2019 with Memorial Sloan Kettering Cancer Center, specializes in developing transformational immunotherapies that improve the body's ability to fight and overcome cancer.

After a record-breaking Series A fundraising round in 2021, Mnemo Therapeutics continues its meteoric rise, choosing to continue its collaboration with Institut Curie. This is another example of the attractiveness and excellence of Institut Curie's research, as well as of the dynamics of our technology transfer strategy, which enables us to detect, develop and bring breakthrough innovations to the market, in order to bring new therapeutic solutions to patients.

said Cécile Campagne, Director of Institut Curie’s Technology Transfer Office and Deputy Director of Carnot Curie Cancer.

The results provide proof of concept for a unique target in glioblastoma, which is currently undergoing experimental validation by Mnemo Therapeutics.

 

[1] Proteogenomics is a field of biological research that uses a combination of proteomics, genomics and transcriptomics to aid in the discovery and identification of peptides.

[2] Since 2016, Mnemo Therapeutics has benefited from the Institut Curie's incubation program with support from the scientific founders in the various stages leading to the creation of the company.

 

References: Single-cell RNA-seq-based proteogenomics identifies glioblastoma-specific transposable elements encoding HLA-I-presented peptides. Pierre-Emmanuel Bonté, Yago A. Arribas, Antonela Merlotti, Montserrat Carrascal, Jiasi Vicky Zhang, Elina Zueva, Zev A. Binder, Cécile Alanio, Christel Goudot, Sebastian Amigorena

 

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