On October 10, 2018 AUM LifeTech, Inc., a Philadelphia-based biotech company, reported that it has partnered with the Children’s Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania to employ next-generation RNA silencing FANA technology as a new approach to cancer immunotherapy designed to treat lung cancer (Press release, AUM Lifetech, OCT 10, 2018, View Source [SID1234529849]). The preclinical results were presented at the 2018 Annual Meeting of the Oligonucleotide Therapeutics Society (OTS) in Seattle, WA.
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The study demonstrated that by reducing levels of a key protein called Foxp3 in immune cells using FANA antisense oligonucleotides (FANA ASOs), a next-generation gene silencing technology, lung cancer survival could be improved. Foxp3 is found in a subset of immune cells called T-regulatory (Treg) cells that constitute 5-10% of T cells (a type of white blood cell). Typically, Tregs suppress inappropriate immune activity and autoimmune diseases, however, their presence in tumors can prove deleterious and promote progression of many types of human cancers. In such cases, Tregs prevent anti-tumor responses by stopping the body’s conventional immune cells from attacking the cancerous cells. Without Foxp3, Treg cells are unable to perform their immune suppressing function. The team showed that FANA ASO therapy effectively reduced the levels of Foxp3 protein in Tregs by silencing Foxp3 gene (messenger RNA or mRNA), thus mitigating Treg-induced immune suppression and allowing the body to mount a full attack on the tumor. "Lung cancer is the biggest killer amongst all cancers. Our preclinical data in a lung cancer animal model is very encouraging and showed complete tumor rejection in a statistically significant animal population that were dosed with FANA antisense oligonucleotide therapy. We are now pursuing the next set of preclinical studies as we move towards filing of an Investigational New Drug (IND) application. I am very thankful to our collaborators and proud of my entire team as we embark on this extraordinary and very important journey to fight cancer," said Veenu Aishwarya, co-founder and Chief Executive Officer of AUM LifeTech, Inc.
This research was co-led by Dr. Wayne Hancock, Chief of the Division of Transplantation Immunology at the Children’s Hospital of Philadelphia. Dr. Hancock, a globally recognized immunologist, is also a Professor of Pathology and Laboratory Medicine at the University of Pennsylvania School of Medicine and has been working in the immune oncology and cancer immunotherapy space for over three decades. "We are very excited about our preclinical data. Tregs are known to suppress anti-tumor responses by host CD8 and CD4 T cells, B cells, NK cells, macrophages and dendritic cells. The ability of FANA ASOs to silence Foxp3 in Tregs makes them very attractive candidates for cancer immunotherapy for lung cancer, especially because currently there are no effective ways to target Tregs. The biggest advantage of FANA ASO therapy is its ability to self-deliver without the need of any formulations," said Dr. Hancock. "There is a lot of enthusiasm in the field of immuno-oncology. Last week’s announcement of the Nobel Prize in Medicine to Dr. James Allison (for CTLA-4) and Dr. Tasuku Honjo (for PD-1) further demonstrates the importance of this field. We plan to use FANA antisense therapy to further advance cancer immunotherapy."
FANA therapy can add significant unprecedented advantages to conventional therapeutic modalities and also target undruggable targets. This is especially beneficial for very aggressive forms of cancer, several of which are difficult to diagnose at early stages. "Existing strategies to treat some forms of cancer include the use of checkpoint inhibitors (monoclonal antibodies) to target immune checkpoints like PD-1 or CTLA-4, which are cell surface proteins involved in regulating the immune system. In other cases, they block the interaction between PD-1 and its ligand PD-L1. Some recent promising strategies include the use of chimeric antigen receptor (CAR) T-cell therapy to treat cancer. Checkpoint inhibitors and CAR T-cell therapy intercept their target at the protein or cellular level respectively. Using FANA ASO therapy, AUM LifeTech has joined the fight against cancer, and is advancing cancer immunotherapy, at the genetic level by directly targeting key genes to achieve anti-tumor immunity," added Aishwarya.
This study used RNA silencing FANA technology which has some key advantages over conventional gene silencing approaches. "I am very happy to see multiple applications of our FANA technology especially in the field of cancer. FANA provides high sequence specificity, stability and efficacy. It has been a long journey for AUM and I am delighted to see that their work is getting ready for clinical applications," said Dr. Masad J. Damha who is Distinguished James McGill Professor at McGill University in Canada. Dr. Damha, an internationally known nucleic acid researcher, serves on the Scientific Advisory Board of AUM LifeTech.
AUM LifeTech has leveraged the space, resources and support of the University City Science Center in Philadelphia since 2013. "The Science Center is delighted to provide the resources and support that allows companies like AUM LifeTech to grow and thrive," said Steve Zarrilli, President & CEO of the University City Science Center. "This promising research and exciting partnership are a reminder of the robust community of innovators that is driving research forward and advancing healthcare in Philadelphia and beyond."