The COVID-19 pandemic is one of modern medicine’s greatest challenges with 20 million (and counting) confirmed cases worldwide. Drugs in development to treat infections span small molecules, vaccines, and antibody-based therapies. Apart from these modalities, scientists are also using regenerative medicine paradigms as inspiration for new cell-based therapies to combat COVID-19.
Earlier in the year, a small pilot study in China showed that COVID patients who were infused with mesenchymal stem cells, or MSCs, had improved outcomes — perhaps due to the ability of stem cells to modulate the immune system. The truth is, we don’t fully know and much of the link between stem cells and COVID remains a gray zone. Nonetheless, MSCs have been given a nod by the US Food and Drug Administration (FDA) under the expanded access compassionate use designation for treating very ill COVID patients.
Since then, the interest in cell therapies to stop COVID infections has only skyrocketed. There are numerous clinical trials currently underway, looking into their safety and potency for reducing the severity of COVID-induced acute respiratory distress syndrome, or ARDS. Here are four major classes of these cell-based approaches for helping patients with COVID and the associated companies to watch.
Mesenchymal stem cells
These stem cells are harvested from the bone marrow, fat, and umbilical cord tissues and can both self-renew and change into specialized cell types. MSCs appear in the majority of ongoing studies for COVID-19 applications. Among the companies working to commercialize MSC-based therapeutics are Mesoblast and Cynata, both based in Australia. The former has one experimental drug product in Phase 3 called Remestemcel-L, cited for use in “moderate to severe ARDS due to COVID-19 infection”.
Likewise, Cynata’s Cymerus™ MSCs have seen some promising results in preclinical studies using a sheep model of ARDS. Here, they report a drop in inflammatory markers in the lung as early as 3 hours after treatment, as well as a reduction in circulatory shock — a life-threatening condition faced by ARDS sufferers associated with dangerously low blood pressure and multiple organ failure.
Natural killer (NK) cells
Natural killer (NK) cells are white blood cells that play a central role in the innate immune system, rushing to the scene when either virus-infected cells or tumor cells are detected and triggering the release of chemicals to destroy the compromised cells. These cellular assassins were particularly attractive in the context of COVID-19, not only for their role in enhancing immune responses, but also for removing lung cells infected by SARS-CoV-2.
New Jersey-based company Celularity has developed an NK-based treatment called CYNK-001, which has been given the all-clear from the FDA for human clinical trials. Celularity’s innovation involves using cells from the postpartum placenta for a range of therapeutic applications, which now includes COVID-19. Earlier studies indicated that those experiencing particularly debilitating forms of COVID-19 may naturally have lower numbers of NK cells and administering CYNK-001 could prevent the infection from worsening.
Cardiosphere-derived cells (CDCs)
CDCs are a lab-derived progenitor cell population from the heart that has been shown to have potent anti-inflammatory and regenerative properties along with the ability to boost the immune system. These are attributed to factors secreted from these stem cells called exosomes. CDCs are a prime candidate for treating COVID-19 patients who are experiencing “cytokine storms”, a result of an extreme, overactive immune response following infection.
Clinical-stage biotechnology company Capricor has CAP-1002 in its pipeline, an “off-the-shelf” CDC therapy for dampening this immune storm in COVID patients. CAP-1002 has already been used with some success in six patients, with follow-up trials investigating the treatment’s immunomodulatory potential in larger cohorts. The company is also developing a potential vaccine for COVID-19 using exosomes as a drug delivery vehicle.
Chimeric antigen receptor T (CAR-T) cells
CAR-Ts are engineered T cells with built-in receptors that hone in on and destroy cancerous cells. These designer T cells were originally created as a therapy for blood cancers. CAR-Ts are already clinically established (with therapies such as Kymriah and Yescarta) and so naturally, scientists were interested in their potential to be redirected towards virally-infected cells in COVID-19.
Cancer patients receiving CAR-T therapies are faced with some serious unwanted side effects including cytokine release syndrome, a flare-up of the immune system. How drug developers will circumvent these risks given that they overlap with the symptoms of ARDS is still unknown. Nonetheless, companies such as AlloVir (in partnership with Baylor College) are joining forces to develop a new CAR-T against the novel coronavirus. Here, T cells will be exposed to fragments from the SARS-CoV-2 virus, which then become the target once infused into patients.
