Could Cell Therapy Be The Answer To COVID-19? – CBS Boston

AgenTus Immune Cell Therapy in Patients with COVID-19

Excessive inflammatory response in the most serious cases of COVID-19, along with surges in infection rates, has caused a healthcare crisis in many countries around the world.

Could cell therapy be the answer?

The public health crisis of COVID-19 has propelled and catalyzed investigations of therapies known to have potential in related disease states for their suitability in combating COVID-19. One such area is immune cell therapy.

To that end, AgenTus Therapeutics, the cell therapy subsidiary of Agenus, an immuno-oncology company advancing immune therapies for patients with cancer, announced the start of a clinical trial with its proprietary allogeneic iNKT cell therapy. iNKT cell therapy has the potential to eliminate the COVID-19 virus, dampen harmful inflammation, and promote protection from reinfection all particularly critical in combating COVID-19. The first patient was treated at Weill Cornell Medical Center and New York Presbyterian Hospital, and early trial results are expected later this year.

Most people who become infected with COVID-19 experience symptoms such as a dry cough and mild fever and recover without medical care, but around 15% develop more serious symptoms including pneumonia and shortness of breath. Approximately 5% of patients with more severe disease experience acute respiratory distress syndrome (ARDS). When this syndrome occurs, the patients lungs become severely inflamed and fluid seeps into the lung tissue from nearby blood vessels, making breathing increasingly difficult. Some of these patients can go on to develop septic shock and multi-organ failure, with more than half dying after reaching this stage.

Respiratory failure from COVID-19 is linked to excessive immune activation that causes a cytokine storm, in which the inflammatory immune protein in the lungs increase to dangerously high levels. This hyper-reaction of the immune system has been observed with other coronaviruses, like SARS and MERS. Cell therapy has previously shown promise for treating respiratory distress for the nearly 500,000 who are affected globally every year even without the COVID-19 pandemic.

Agenus, a US-based biotechnology company headquartered in Lexington, MA with the goal of advancing immune therapies for patients with cancer, recently announced that its proprietary allogeneic iNKT cell therapy will be evaluated for its potential to treat COVID-19 and cancer through its cell therapy subsidiary, AgenTus.

Invariant natural killer T cells (iNKT cells) are a unique cell type that combine features of two critical arms of the immune system, T cells (adaptive immunity) and NK cells (innate immunity), making them invaluable in combatting diseases like cancer and COVID-19. In the case of cancer, they travel to tumor tissue by detecting a protein known as CD1d. They also 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. In preclinical models, iNKT cells have been shown to work alone and have also demonstrated curative potential when activated and combined with Agenus pipeline of immuno-oncology drug candidates.

Agenus has observed that the number of iNKT cells in the body is reduced in people with cancer and infectious diseases like COVID-19, and this reduction is associated with poorer response to disease. In preclinical models that bear similarities to SARS-COV-2, increasing the number or frequency of iNKT cells reduced viral shedding and prevented inflammation-driven lung injury. These specific attributes are of paramount importance in any therapy attempting to overcome COVID-19.

As a result of this research, AgenTus is advancing an iNKT cell therapy program towards clinical trials in both cancer and COVID-19. Beyond the curative potential of iNKT cells as addressed above, AgenTus cell therapy program has the potential to be more practical and more beneficial than currently approved cell therapies. Currently approved cell therapies require genetic manipulation, which increases their cost, manufacturing time and complexity. On the other hand, iNKT cells may be effective even without genetic manipulation and have the potential to be manufactured to treat large numbers of patients from a single batch, presenting the opportunity for lower costs. Further, iNKT cells have been tested in clinical trials and have been well-tolerated, thus decreasing the risk of serious side effects.

Encouraged by these compelling properties of this cell therapy, AgenTus announced today the start of a clinical trial to test iNKT cells in patients with moderate to severe symptoms of COVID-19. The study is being led by Dr. Koen van Besien, M.D., Ph.D., Professor of Medicine and Director of the Stem Cell Transplant program at Weill Cornell Medical Center and New York Presbyterian Hospital. The trial is designed to evaluate the benefit of infusing iNKT cells in patients who have moderate to severe symptoms of COVID-19. The outcome of the trial will provide insight into whether administering iNKT cells will help to eliminate the virus, dampen harmful inflammation, and promote protection from reinfection.

As mentioned earlier, iNKT cell therapy offers promise for the fight against cancer as well as the fight against COVID-19. To that end, Agenus is also advancing iNKT cells into clinical trials for patients with cancer. Agenus recently presented data at two major cancer conferences, the Society of Immune Therapy for Cancer (SITC; #SITC19) and the American Association of Cancer Research (AACR; #AACR20), which revealed that in preclinical models AgenTus iNKTs can penetrate tissues, giving them a critical advantage in targeting solid tumors not currently served by approved cell therapies. These data also showed that the combination of checkpoint antibodies and iNKT cell triggering therapy shows curative potential in cancer models that are refractory to available therapies.

Agenus is the only company known to have a portfolio of checkpoint antibodies, cell therapy, and cancer vaccines. This gives the company enormous flexibility to develop novel combinations of agents with curative potential for patients with cancer and infectious disease at a significant cost advantage.

The potential benefits of iNKT cell therapy against both COVID-19 and cancer thus look very promising. Agenus is excited to investigate the possibilities of these treatments against these diseases that cause suffering and death for thousands of patients every year. By leveraging its unique capabilities and extensive pipeline against these diseases, Agenus hopes to provide significant benefit to these patients and a potential path to a cure.




3) Exley et al., Clinical Cancer Research, 2017.

4) Tanne et al., American Association of Cancer Research, 2020.

5) Mavers et al., Frontiers in Immunology, 2017.

6) Nair and Dhodapkar, Frontiers in Immunology, 2017.

7) Wolf et al. Frontiers in Immunology, 2018.

8) Burcu et al., Society for Immunotherapy of Cancer, 2019.

_______________________________________________________________________________________________________________ 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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Could Cell Therapy Be The Answer To COVID-19? - CBS Boston

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