Results published in peer-reviewed Cancer Research share novel insights into Chi3L1’s role in modulating Glioma stem cells and reinforces the potential therapeutic impact of Anti-Chi3L1
Providence, RI, April 27, 2023 (GLOBE NEWSWIRE) — Ocean Biomedical (NASDAQ: OCEA), a biopharma company working to accelerate the development and commercialization of scientifically compelling assets from research universities and medical centers, announced today that its Scientific Co-founder, Jack A. Elias, MD, published new findings in the peer-reviewed journal Cancer Research that detail the mechanisms behind the role of chitinase 3-like-1 (Chi3L1) in the growth of glioblastoma tumors, providing further evidence of the potential impact of Ocean’s anti-Chi3L1 antibody in suppressing severe glioblastoma tumor growth.
Results of the research conducted at the Laboratory of Cancer Epigenetics and Plasticity at the Lifespan Health System and Brown University, showed that an independent team led by molecular neuroscientist Nikos Tapinos, MD, PhD, was able to uncover new data on the efficacy of Ocean Biomedical’s anti-Chi3L1 antibody in human glioblastoma implanted mouse models, resulting in clear reduction in glioblastoma tumor growth.
The paper also revealed groundbreaking insights into the mechanisms underlying stem cell differentiation in glioma stem cells, and how that differentiation process is altered by Ocean Biomedical’s cancer therapeutic candidate. In two different study approaches, treatment with anti-Chi3L1 antibody in vivo resulted in over 60% reduction of human glioblastoma growth, and significant survival benefit. This can be seen in the MRI evaluations of the human tumors in the brains of mice (which appear in red) and the quantitation of tumor volume from these scans (see figures). This represents a medical breakthrough in understanding how the most aggressive glioblastoma tumors are formed, and how patients diagnosed with this challenging disease might possibly be treated.
“This is a completely new way of thinking about how to treat this tumor. Glioblastoma is so challenging partly because the cells adapt to the environment constantly – but if you block Chi3L1 they can’t seem to acquire the more aggressive mesenchymal phenotype. It gives us a clear path forward to being able to address glioblastoma with this novel approach,” said Dr. Nikos Tapinos MD, PhD, Director of the Laboratory of Cancer Epigenetics and Plasticity, and last author on the paper.
This targeted research data builds on prior discovery work by Dr. Jack A. Elias, who is the former Dean of Medicine and Biology, and Senior Vice President for Health Affairs at Brown University and former Chair of Medicine and Chief of Pulmonology and Critical Care Medicine at Yale University and Yale-New Haven Hospital. Over the last year, Dr. Elias has published discoveries about the roles of CHI3L1 in the pathogenesis of a wide variety of cancers. He has also previously revealed discoveries that demonstrate that the metastasis of malignant melanoma cells can be inhibited by targeting immune checkpoint inhibitors (ICPI) such as PD-1 and CTLA-4 and their ligands. The novel approach to tumor suppression being advanced by Ocean Biomedical is focused on simultaneously impacting multiple cancer pathways including those mediated by PD-1, CTLA4 by controlling CHi3L1, PD-1, PD-L1, CTLA-4, other immune checkpoint inhibitors, and T-cell co-stimulators. It has been known for a long time that optimal antitumor responses frequently require the simultaneous administration of more than one therapy.
“We are excited that, step by step, we are gaining a deeper understanding of the multiple effects that CHi3L1 has in oncogenesis,” commented Dr. Elias, “This antibody is very effective – every time we put it into an appropriate modeling system we get exciting results such as the findings in these two human-mouse GBM studies. Glioblastoma is a major area of unmet medical need, and these new studies are highly encouraging because they open the door to a new way of treating this devastating cancer.”
“We are pleased to see our glioblastoma candidate being validated by Dr. Tapinos and his team, and we hope this will be another step in moving us towards filing an IND for Glioblastoma,” said Elizabeth Ng, CEO of Ocean Biomedical.
Ocean’s Chairman and co-founder, Dr. Chirinjeev Kathuria added, “There are so many challenges around finding effective treatments for glioblastoma, and we are working to advance this new approach that we believe can give hope to patients with glioblastoma, and can also be extended to potential therapeutics for non-small cell lung cancer, melanoma, and other forms of cancer.”
Prior research has established that elevated Chi3L1 levels are associated with many cancers, including glioblastoma, and may be targeted therapeutically. Recent studies from Ocean Biomedical have demonstrated that CHI3L1 is a critical regulator of a number of key cancer-causing pathways, highlighting its ability to inhibit tumor cell death (apoptosis), its inhibition of the expression of the tumor suppressors P53 and PTEN and its stimulation of the B-RAF protooncogene. Most recently Dr. Elias’s research team has discovered that CHI3L1 is a “master regulator” of ICPI, including key elements of the PD-1 and CTLA4 pathways. In accord with the importance of these pathways, Ocean has also generated antibodies: 1.) a monoclonal antibody against CHI3L1, 2.) bispecific antibodies that simultaneously target CHI3L1 and PD-1, and 3.) a new bispecific antibody that simultaneously targets CHI3L1 and CTLA4. The impressive ability of these bispecific antibodies to control primary and metastatic lung cancer in murine experimental modeling systems have been discussed in detail in an earlier article in the Journal of Clinical Investigation, and this expanded approach in Frontiers in Immunology.
Suren Ajjarapu, an Ocean Biomedical Director commented, “We’re proud to be collaborating with some of our nation’s top scientists to move these important programs forward, and we are confident that each advancement will add long term value for our shareholders and for the doctors and patients who need innovative new treatments.”
Discussing the future direction of his work Dr. Tapinos said, “Now we know which proteins are expressed in response to Chi3L1, which are different in different subpopulations of cells, with Chi3L1 common to all of them. They just receive it in different ways and upregulate different pathways. Knowing the drivers for this heterogeneity, this is the holy grail for glioblastoma.”
About Ocean Biomedical
Ocean Biomedical, Inc. (“Ocean Biomedical” or the “Company”) is a Providence, Rhode Island-based biopharma company with an innovative business model that accelerates the development and commercialization of scientifically compelling assets from research universities and medical centers. Ocean Biomedical deploys the funding and expertise to move new therapeutic candidates efficiently from the laboratory to the clinic, to the world. Ocean Biomedical is currently developing five promising discoveries that have the potential to achieve life-changing outcomes in lung cancer, brain cancer, pulmonary fibrosis, and the prevention and treatment of malaria. The Ocean Biomedical team is working on solving some of the world’s toughest problems, for the people who need it most.
To learn more, visit www.oceanbiomedical.com.
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