Bernard A. Fox: Back in Taiwan – Sharing the Next Frontier in Cancer Immunotherapy at Grand Rounds
Bernard A. Fox, Co-Founder/President/CEO at UbiVac, shared a post on LinkedIn:
“Thrilled to be back in Taiwan and reconnecting with both old and new friends.
Yesterday’s visits to National Taiwan University Hospital and the Cancer Center were inspiring—I had the pleasure of meeting several outstanding fellows and faculty members. Today, I’m looking forward to presenting at Grand Rounds. The focus of my talk is what I consider the third major wave in the renaissance of cancer immunotherapy.
The first wave, beginning around 2010, was driven by checkpoint inhibitors.
The second wave brought us CAR-T cell therapy.
Now, we are entering the third wave: targeting cancer’s Dark Proteome or Dark Matter.
The Earle A. Chiles Research Institute and Providence Cancer Institute, in collaboration with UbiVac, have developed a novel immunotherapy, DPV-001, that targets this Dark Matter. In a trial led by Dr. Rom Leidner, when DPV-001 was combined with checkpoint blockade, this approach tripled the response rate in patients with recurrent/metastatic head and neck cancer (HNSCC)—a study supported by Incyte.
But what exactly is cancer’s Dark Matter?
Cancer’s Dark Matter or Dark Proteome are peptides presented by HLA molecules on the surface of cancer cells, derived not from mutated genes, but many from short-lived, non-mutated proteins encoded by the Dark Genome. Many of these proteins aren’t expressed in the thymus and often go unrecognized by the immune system—until now.
Recent studies in Science and Springer Nature Cancer (by teams in Boston and Montreal) have shown that Dark Genome–derived antigens vastly outnumber classic mutated neoantigens on the surface of cancer cells, offering a rich new target space for immunotherapy.
Building on foundational work from jonathan yewdell at NIAID and more recent contributions from Perreault Claude, Pierre Thibault William Freed-Pastor, Michal Bassani-Sternberg, Catherine Wu, Aviv Regev, and others, we believe we now have the first in vivo–derived T cell receptor (TCR) specific for a Dark Matter antigen found in our complex multi-antigen vaccine, DPV-001.
This TCR recognized an antigen expressed by the patient’s tumor. This same peptide was also found to be presented by other HNSCC, NSCLC, and pancreatic cancer cell lines. Remarkably, this patient is now a 10-year survivor, providing long-term safety data for a TCR-based approach to these diseases.
Though early, the promising clinical data, coupled with data from on-treatment serial biopsies —point toward opportunities to enhance both response rate and durability. Looking forward to exploring opportunities to partner and expand access of DPV-001 to Taiwan and other parts of the world!
Providing two amazing papers from William Freed-Pastor and Perreault Claude.”
Title: Tumor antigens preferentially derive from unmutated genomic sequences in melanoma and non-small cell lung cancer
Journal: Nature Cancer
Authors: Anca Apavaloaei, Qingchuan Zhao, Leslie Hesnard, Maxime Cahuzac, Chantal Durette, Jean-David Larouche, Marie-Pierre Hardy, Krystel Vincent, Sylvie Brochu, Jean-Philippe Laverdure, Joël Lanoix, Mathieu Courcelles, Patrick Gendron, Mathieu Lajoie, Maria Virginia Ruiz Cuevas, Eralda Kina, Julie Perrault, Juliette Humeau, Grégory Ehx, Sébastien Lemieux, Ian R. Watson, Daniel E. Speiser, Michal Bassani-Sternberg, Pierre Thibault, Claude Perreault
Title: Pancreatic cancer-restricted cryptic antigens are targets for T cell recognition
Journal: Science
Authors: Zackery A. Ely, Zachary J. Kulstad, Gurcan Gunaydin, Sudarsana Addepalli, Eva K. Verzani, Marta Casarrubios, Karl R. Clauser, Xilin Wang, Isabelle E. Lippincott, Cedric Louvet, Thomas Schmitt, Kevin S. Kapner, Miles P. Agus, Connor J. Hennessey, James M. Cleary, Sine R. Hadrup, Susan Klaeger, Jennifer Su, Alex M. Jaeger, Brian M. Wolpin, Srivatsan Raghavan, Eric L. Smith, Philip D. Greenberg, Andrew J. Aguirre, Jennifer G. Abelin, Steven A. Carr, Tyler Jacks, William A. Freed-Pastor
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