-Studies are the first to confirm TE-exon splicing junctions can help differentiate tumors from healthy tissue, potentially solving a longstanding challenge for the field of immuno-oncology-
-Results further confirm "grey genome" can be mined for meaningful cancer targets, offer a modality-agnostic approach to identify tumor specific antigens-
PARIS, Feb. 3, 2023 /PRNewswire/ -- Mnemo Therapeutics, a biotechnology company developing transformational immunotherapies, has announced publication of two groundbreaking scientific studies developed at Institut Curie, its closest academic collaborator, in the journal Science Immunology. The publications reveal TE-exon splicing junctions act as a source of novel recurrent, cancer-specific targets and have potential implications for developing more effective and less toxic immunotherapies. The findings presented further validate Mnemo's antigen discovery platform.
The "grey genome," also known as the part of the dark genome that is annotated, transcribed and sometimes translated, accounts for approximately 45% of the total human genome. These genomic regions were historically disregarded because they are poorly understood; however, a recent growing body of evidence hints that probing the grey genome could expand the potential universe of previously unknown targets by identifying features that encode for cancer-specific targets that are both tumor-specific and shared by significant proportions of patients.
"Current cancer targets originate from a very small percentage of the human genome, leaving regions with potential oncology targets largely overlooked," said Robert LaCaze, CEO of Mnemo Therapeutics. "By mining the grey genome, the authors have uncovered an entirely new class of cancer antigens that are highly tumor-specific and recurrent in cancer patients. We are eager to not only better understand how these new tumor antigens synergize with our current pipeline, but also the ways they might be further leveraged as part of strategic partnerships to advance the broader immuno-oncology field."
In the first study*, directed by Sebastian Amigorena, Ph.D., Senior Vice President, Immunology, and scientific co-founder of Mnemo, CNRS Research Director and head of the Immune Responses and Cancer team (Institut Curie/Inserm), and Marianne Burbage, Ph.D., Inserm Researcher on the team, researchers identified a new family of antigens derived from non-canonical splicing junctions in mouse tumor cell lines. These antigens prompt an immune response in tumor-bearing mice and successfully delayed tumor growth when these peptides were administered as prophylactic or therapeutic vaccines. Additionally, inactivation of Setdb1, a histone methyltransferase, resulted in increased expression of this family of antigens and tumor cell immunogenicity (the ability to trigger an immune response that stops tumor growth).
The second study**, led by Amigorena and Joshua Waterfall, Ph.D., head of the Integrative Functional Genomics of Cancer team (Institut Curie/Inserm), specifically examined this family of antigens in non-small cell lung cancer (NSCLC) patient and healthy tissue samples. The team identified tumor-specific non-canonical splicing junctions that generated immunogenic peptides in NSCLC patients, thus describing a new source of recurrent, tumor-specific antigens in NSCLC cancer patients.
"Identifying targets that are unique to cancer cells and absent from healthy tissue has been a major barrier to developing more successful immunotherapies," said Amigorena. "The collective findings advance our knowledge of tumor-specific antigens, unlocking new possibilities for the treatment of cancer not only in the cell therapy space, but across multiple approaches and modalities."
*Burbage M., Rocañín-Arjó A., Baudon B., Arribas Y.A., Merlotti A., Rookhuizen D.C., Heurtebise-Chrétien S., Ye M., Houy A., Burgdorf N., Suarez G., Gros M., Sadacca B., Carrascal M., Garmilla A., Bohec M., Baulande S., Lombard B., Loew D., Waterfall J.J., Stern M-H., Goudot C., Amigorena S. Epigenetically-controlled tumor antigens derived from splice junctions between exons and transposable elements. Science Immunology. 2023 February. https://www.science.org/doi/10.1126/sciimmunol.abm6360
**Merlotti A., Sadacca B., Arribas Y.A., Ngoma M., Burbage M., Goudot C., Houy A., Rocañín-Arjó A., Lalanne A., Seguin-Givelet A., Lefevre M., Heurtebise-Chrétien S., Baudon B., Oliveria G., Loew D., Carrascal M., Wu C.J, Lantz O., Stern M-H., Girard N., Waterfall J.J., Amigorena S. Non-canonical splicing junctions between exons and transposable elements represent a source of immunogenic recurrent neo-antigens in lung cancer patients. Science Immunology. 2023 February. https://www.science.org/doi/10.1126/sciimmunol.abm6359
About Mnemo Therapeutics
Mnemo is driven to create powerful immunotherapies to improve the body's ability to detect and eradicate cancer. A lack of cancer-specific targets, coupled with lack of long-term persistence and sensitivity, create significant challenges in the field of immuno-oncology. Mnemo is committed to addressing these problems and engineering the future of immunotherapies to transform the lives of people with cancer through the discovery of novel cancer-specific targets, while boosting immune activity to treat solid tumors. Mnemo is headquartered in Paris and 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.
About Institut Curie
Institut Curie, France's leading cancer centre, combines an internationally renowned research centre with a cutting-edge hospital group, which treats all types of cancer, including the rarest. Founded in 1909 by Marie Curie, Institut Curie employs 3,700 researchers, physicians and health professionals across three sites (Paris, Saint-Cloud and Orsay), all of whom contribute to its three missions of treatment, research and teaching. As a private foundation recognised as a public utility, Institut Curie is authorised to accept donations and bequests, and thanks to the support of its donors, is able to accelerate discoveries and improve patient treatment and quality of life.
For more information: www.curie.fr
Since 2011, Institut Curie is certified as "Institut Carnot Curie Cancer". The Carnot label is a label of excellence awarded to academic research structures that have demonstrated quality and involvement in collaborative research. Curie Cancer offers industry partners the opportunity to set up research collaborations and benefit from the expertise of Institut Curie teams for the development of innovative treatment solutions for cancer, from biological target to clinical validation. Curie Cancer is a member of the Carnot FINDMED network, a group of 13 Carnot institutes, in order to facilitate access to their technology platforms and innovation capabilities for very small and medium-sized companies, SMEs and SMIs in the pharmaceutical industry.
For more information: http://www.instituts-carnot.eu/fr/institut-carnot/curie-cancer - https://findmed.fr
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