Mnemo Therapeutics, a biotechnology company developing transformational immunotherapies, announced a publication in Cell Reports that demonstrates peptides derived from transposable elements (TEs) – mobile regions of DNA that move to other areas of the genome – may represent cancer-specific targets for immunotherapy. The article is authored by a team of researchers working under the leadership of Sebastian Amigorena, Ph.D., CNRS research director, scientific co-founder of Mnemo and head of the Immune Responses and Cancer Team at Institut Curie (Immunity and Cancer Unit – Institut Curie/Inserm). Landmark Publication Further Validates Approach to Expand the Potential Universe of Cancer-specific Targets by Probing the “Grey Genome”
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“Mnemo is committed to comprehensively tackling the challenges facing immunotherapies, including the lack of suitable cancer-specific targets,” said Mnemo Chief Executive Officer, Robert LaCaze. “We are extremely encouraged by the data put forth in this publication which validates our unique target ID approach and informs the future of Mnemo’s science.”
Traditionally, the human genome has been broadly broken down into two main categories – the 4%, known to encode for proteins, and the 96%, with elements either noncoding and/or poorly understood, also known as the “dark genome.” The data demonstrated in this publication provides compelling evidence to suggest that novel cancer targets can be found outside of the 4%, necessitating the expansion of our definition to include the “grey genome.” The “grey genome”, which accounts for around 45% of the human genome, is composed of TEs, long non-coding RNAs and a few other non-coding transcripts. Increased transcription of TEs is found to occur in some tumor cells, suggesting they may encode for cancer antigens. The publication, titled, “Single-cell RNA-seq-based proteogenomics identifies glioblastoma-specific transposable elements encoding HLA-I-presented peptides,” explored this connection, demonstrating that these DNA features may hold the key to unlocking new targets for immunotherapy.
“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,” said Dr. Amigorena. “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.”
In this study, researchers leveraged a sophisticated proteogenomic approach to explore the grey genome, in a search to uncover TE-derived peptides that can act as suitable cancer targets.