On January 30, 2023 Ocean Biomedical and Aesther Healthcare Acquisition Corp. (NASDAQ: AEHA) reported the discovery of a second major anti-tumor pathway and therapeutic approach that targets CTLA-4, inhibiting the metastasis of malignant melanoma cells to the lung using a novel bispecific antibody approach (Press release, Ocean Biomedical, JAN 30, 2023, View Source [SID1234626638]). This major regulating mechanism discovery, recently published in Frontiers in Immunology, by Ocean Biomedical’s Scientific Co-founder and Brown University’s Emeritus Dean of Medicine and Biological Sciences, Dr. Jack A. Elias, builds on his team’s prior discoveries that target Chitinase 3-like-1 (CHI3LI) and its role in inhibiting T-cell proliferation. Additionally, this promising research reveals a third anti-tumor pathway targeting T-cell co-stimulation using the inducible co-stimulator (ICOS) and its ligand ICOSL, and Cluster of Differentiation 28 (CD28) and its ligands B7-1 and B7-2. Ocean Biomedical’s novel approach to tumor suppression, focused on controlling CHI3LI, other immune checkpoint inhibitors, and T-cell co-stimulators, has potential application for tumor suppression across multiple cancer pathways.
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"If you control CH3L1, you don’t just control one anti-cancer pathway, you simultaneously control many anti-cancer pathways. This is an unprecedented leap forward and we are very pleased at the spotlight that Frontiers in Immunology has placed on it," commented Dr. Jack A. Elias, Scientific co-founder. "In searching for and narrowing in on major pathways that are applicable across cancer types, we are making discoveries that will drive cancer research, and eventually treatment and patient outcomes, forward."
"We are excited to extend the tumor-control application of Dr. Elias’ discovery that CHI3L1 is a critical regulator of T-cell activity. These therapies have the potential to save lives of people affected not just by lung metastasis, and melanoma, but also non-small cell lung cancer, glioblastoma and other forms of cancer," said Dr. Chirinjeev Kathuria, co-founder and Executive Chairman.
Malignant melanoma, a very serious skin cancer with a 22.5% five-year survival for patients with Stage IV disease, can metastasize to other organs. Once it has spread to other organs, it is difficult to treat – in some cases, it can spread to the lungs and result in non-small cell lung cancer (NSCLC), a major unmet medical need that accounts for 85% of pulmonary malignancies and affects approximately 450,000 individuals. In over 50% of affected NSCLC patients, tumors are not diagnosed until the advanced stages, with metastatic spread that precludes curative surgical resection.
Recent studies of NSCLC have highlighted the effectiveness of immune checkpoint inhibitor (ICPI), therapies that block cancer-proliferating proteins like CHI3L1 and help the patient’s body recognize and attack cancer cells. Unfortunately, only a minority of patients respond to these therapies and the responses are often not durable.
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, Chairman and CEO of Aesther, commented, "Immunotherapy is the future of cancer care, and Aesther is proud to be partnering with Ocean Biomedical in advancing the development of their cancer treatments, along with their fibrosis treatments, and their global malaria program. We look forward to working with Ocean Biomedical to bring all of these therapies to patients, for the long-term shareholder value and the continued advancement of medical science."