COVID-19 has caused a global healthcare crisis and cancer persists as a leading cause of death worldwide
Could cell therapy be the answer for both?
The public health crisis of COVID-19 has propelled and catalyzed investigations of therapies suspected to have potential for combating COVID-19. At the same time, the search for optimal cancer treatments and a potential cure for this deadly disease continues. Immunotherapy shows promise for groundbreaking results in both these diseases. Could AgenTus’ iNKT cell therapy be a solution to these critical problems?
The Power of iNKT Cells
Invariant natural killer T cells (iNKT cells) are a unique cell type of the human immune system that combines features of cells from both arms of the immune system: T cells (adaptive immunity) and NK cells (innate immunity). It has been observed that the number of iNKT cells is reduced in patients with cancer and infectious diseases like COVID-19, resulting in an inadequate immune response against the invading pathogen. Administration of AgenTus’ iNKT cell therapy, AgenT-797, increases the number of iNKTs in the body, which is expected to enhance appropriate immune response against the infection or disease.
Beyond the curative potential of iNKT cells, AgenTus’ cell therapy program could be more practical and accessible than currently approved cell therapies. Current therapies rely on genetic manipulation, lengthy manufacturing timelines, and high cost; they have also had safety complications in the clinic. On the other hand, iNKT cells are expected to be effective without genetic manipulation and can be manufactured to treat large numbers of patients from a single batch, presenting the opportunity for low-cost administration. Further, iNKT cells have already been tested in other clinical trials and have been well-tolerated, suggesting a lower risk of serious side effects than seen with other cell therapies.
iNKT Cell Therapy Against COVID-19
Nearly 15% of patients diagnosed with COVID-19 develop serious symptoms including pneumonia and difficulty breathing. Approximately 5% of these patients with more severe cases experience acute respiratory distress syndrome (ARDS), which can lead to respiratory failure and death. This severe condition is linked to excessive immune activation that causes a condition called “cytokine storm,” in which the inflammatory immune protein in the lungs increases to dangerously high levels. While hyper-reaction of the immune system has also been observed with other coronaviruses, like SARS and MERS, the COVID-19 virus has elevated its threat to the levels of the current global pandemic. Cell therapy has already shown promise for treating respiratory distress syndrome, leading to the expectation that it will also be effective in the case of respiratory distress caused by COVID-19.
Activated iNKTs elicit a rapid anti-viral response via multiple mechanisms. These include the activation and regulation of other essential immune cells such as NK cells, T cells, and B cells. Mobilization of these cells is crucial for an effective response against viral infections. iNKT cells also have the ability to reduce the potentially lethal complications of cytokine storm implicated in respiratory distress. In preclinical models representative of COVID-19, activated iNKT cells have been shown to specifically migrate to areas of infection such as the lungs. This migration leads to a decrease in viral titers and prevents lung injury by reducing the number of inflammatory cells. iNKT cell therapy thus has the potential to eliminate the COVID-19 virus, dampen harmful inflammation, and promote protection from reinfection. These specific attributes are of paramount importance in any therapy attempting to overcome COVID-19.
Propelled by these observations, AgenTus Therapeutics, the cell therapy subsidiary of Agenus, a US-based biotechnology company headquartered in Lexington, MA with the goal of advancing immune therapies for patients with cancer and infectious diseases, is advancing a clinical trial for its proprietary allogeneic iNKT cell therapy to treat critically ill, intubated COVID-19 patients. They are being treated at Weill Cornell Medical Center and New York Presbyterian Hospital, and preliminary results from the Phase 1 trial reveal that the therapy can be administered tolerably. To our knowledge, this is the only clinical trial of allogeneic unmodified iNKT cells in patients with COVID-19. Dose escalation is expected to be completed in the first half of 2021, for an initiation into a Phase 2 trial with data readouts expected in the fourth quarter of this year.
iNKT Cells in the Fight Against Cancer
iNKT cell therapy offers promise for the fight against cancer as well as the fight against COVID-19. In the case of cancer, iNKT cells both directly target tumors and also reshape the tumor microenvironment to promote an enhanced immune response. iNKT cells travel to tumor tissue by detecting a protein expressed on these tumors known as CD1d. Additionally, iNKT cells themselves express a protein known as NKG2D, which recognizes tumor stress ligands. Importantly, these proteins are expressed in both solid and liquid tumors, making iNKT cells broadly applicable to all cancer patients. Upon recognition, iNKTs can directly kill the tumor cells through their cytotoxic abilities. They can also recruit nearby effector cells to further enhance their anti-tumor activity.
Agenus has presented data at two major cancer conferences, the American Association of Cancer Research (AACR) in April 2020, and the Society of Immune Therapy for Cancer (SITC) in November 2020, supporting this science and revealing that, in preclinical models, AgenTus iNKTs demonstrate potent tumor killing.  These cells promote an immune response against cancer through various mechanisms, making them invaluable for combating this disease. These data also demonstrated that iNKT cells can penetrate tissues, making them effective against solid tumors as well as liquid tumors, unlike currently approved cell therapies. Data further showed that the combination of checkpoint antibodies and iNKT cell triggering therapy has curative potential in cancer models that are resistant to currently available therapies.
Encouraged by the compelling properties of its cell therapy, AgenTus announced today the start of a clinical trial to test iNKT cells in patients with cancer. The study is being led by Clifton Mo, M.D., at the Dana-Farber Cancer Institute in Boston, MA. The trial will focus on treating patients with hematologic cancers and solid tumors and is designed to evaluate the safety and efficacy of iNKT cell therapy in these patients.
The potential benefits of iNKT cell therapy against both COVID-19 and cancer look promising. Agenus is excited to investigate the potential of these treatments against these diseases that cause suffering and death for thousands of patients every year. Agenus is the only company known to have a portfolio of checkpoint antibodies, cell therapy, adjuvants, and cancer vaccines. This comprehensive portfolio gives the company enormous flexibility to develop novel combinations of agents with curative potential for patients with cancer and infectious diseases at a significant cost advantage. By leveraging its unique capabilities and extensive pipeline, Agenus hopes to provide significant benefit to patients and a potential path to a cure.
Forward-Looking Statements: This article includes forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding Agenus and AgenTus’ abilities to produce effective allogeneic cell therapies to treat solid tumors, the anticipated clinical benefits and costs of such cell therapies, and future clinical development and regulatory plans. These statements are subject to risks and uncertainties, including those described in Agenus’ SEC filings.
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