Landmark Publication Further Validates Approach to Expand the Potential Universe of Cancer-specific Targets by Probing the "Grey Genome"
Results provide foundational proof-of-concept for a unique target ID in glioblastoma, build further confidence in Mnemo's EnfiniT Discovery Engine
PARIS, June 9, 2022 /PRNewswire/ -- Mnemo Therapeutics, a biotechnology company developing transformational immunotherapies, today 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).
"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. Additional results are outlined below.
- The authors obtained single-cell resolution of TEs, distinguishing between different cell populations in the tumor microenvironment.
- Concurrently, the authors demonstrated differential expression of these TEs in glioblastoma over healthy tissue.
- 370 HLA-I-bound peptides derived from TEs were identified, making them visible to the immune system and therefore potential targets for immunotherapies.
- Furthermore, an in vitro experiment leveraging TE-peptide loaded cells and healthy T cells showed an immunogenic response, illustrating the promise of these peptides as possible therapeutic targets.
"While initially tested in glioblastoma, this approach is applicable across cell-types, laying the groundwork for its application in other cancer models for indication-specific antigen identification," Mnemo Co-Founder and Chief Operating Officer, Alain Maiore. "This research further validates Mnemo's EnfiniT Discovery Engine, which aims to overcome the key challenges facing current immunotherapies by enhancing therapeutic precision, durability, and potency."
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.
Mnemo is developing transformational immunotherapies to improve the body's ability to fight and overcome cancer. Integral to Mnemo's approach is the EnfiniT Discovery Engine, composed of key technologies that work to identify novel cancer-specific antigens and enhance immune cells' memory and persistence. Mnemo will harness these technologies with multiple modalities across a range of oncology indications, engineering the future of immunotherapies to transform the lives of people with cancer. Mnemo is headquartered in Paris with an office in New York City, and it maintains state of the art laboratories in Paris, New York, and Princeton, New Jersey. The company leverages an international talent pool and global resources in its quest to create immunological cures.
To learn more, visit https://mnemo-tx.com and follow Mnemo Therapeutics on Twitter (@MnemoTx) and LinkedIn.
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SOURCE Mnemo Therapeutics
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