Cell and gene therapies have made impressive progress in recent years but have rarely grabbed the headlines. Now the coronavirus pandemic, and the race to develop vaccines and treatments, have pushed them into the global spotlight. Advocates say that their potential efficacy, and the speed with which testable doses can be developed, may give them the edge over more conventional approaches.
Most of the 180 vaccines listed by the World Health Organization as in development use techniques that are also deployed in gene and cell therapies. They include the vaccines being developed by Moderna and Pfizer, as well as the Oxford university-AstraZeneca vaccine whose trials were paused last week.
In vaccines for new viruses, the priority is to produce something quickly that works, says Luk Vandenberghe, associate professor at Harvard Medical School. “The appeal of gene-based vaccines is nimbleness, responsiveness and speed of development,” he says.
Once clinical trials reveal which fast-track vaccines are most effective, Prof Vandenberghe says, the question then will be how quickly the global population can be immunised. “This includes how durable the immune responses are, how quickly the vaccines can be manufactured, and how stable the product is, particularly for developing countries where supply and distribution can be challenging,” he says.
Several fast-track vaccines under development rely on a common type of virus called adenovirus to deliver the genetic material that will prime the body to resist coronavirus. But adenovirus can also induce an excessive immune response, says Prof Vandenberghe.
His team is gearing up for clinical trials of an alternative vaccine based on a gene therapy that is used in treatments for neurological and genetic diseases, where the delivery mechanism is a so-called adeno-associated virus, or AAV.
The vaccine is already being produced for clinical study by manufacturers such as Novartis Gene Therapies, and its genetic payload can be tailored within weeks to deal with any new strains of coronavirus that emerge. “The pre-clinical data from animal trials look very encouraging,” Prof Vandenberghe says.
Other cell-therapy researchers are looking at ways of helping patients who have already contracted Covid-19. A particular focus is acute respiratory distress syndrome (ARDS), which is triggered by an excessive immune response. This creates a “cytokine storm”, where the levels of inflammatory immune proteins become dangerously high, causing severe damage to the lungs.
ARDS has a high mortality rate and can be caused by pneumonia, sepsis and trauma. In the case of Covid-19, it is the reason patients often need a ventilator. But its effects could be suppressed by treatments based on mesenchymal stromal cells (MSCs). Derived from human tissue such as bone marrow or umbilical cord, these are a kind of stem cell, which means they can morph into other types of tissue — potentially enabling them, for example, to replace damaged lung cells.
A team at Queen’s University Belfast has begun a clinical trial of MSCs aimed at confirming they are safe and effective — for example, by improving patients’ oxygenation levels so they can come off ventilators more quickly, and enabling better recovery of other organs such as kidneys.
“We are ahead of the game, because we were just starting a study on this particular type of MSC in non-Covid-related ARDS when the pandemic began,” says Professor Cecilia O’Kane, from the Wellcome-Wolfson Institute for Experimental Medicine at Queen’s. Trial approvals were in place, so when the pandemic struck the team was able to immediately refocus its study on Covid-19.
The team has recruited 14 of the 60 patients it hopes to sign up across the UK. As with other trials, progress will depend on how rapidly the pandemic spreads, but the aim is to complete the study by the end of next year.
“We will follow these people up for two years after they receive the cells, so we’ll have a better idea of what happens beyond the hospital discharge period, whether they have a better quality of life afterwards, and whether any concerns arise at a later stage,” Prof O’Kane says.
Adam Barker, healthcare equity analyst at Shore Capital, estimates some 40 trials of MSCs are under way for Covid-19. “The data from human studies of MSCs for pneumonia and influenza suggest they are generally safe and may reduce the risk of death, albeit the data are not conclusive,” he says.
“The other hope is that they might help tissue regrow — that potential regenerative capacity, which is the holy grail of stem cell medicine,” he adds.
Athersys, in Cleveland, Ohio, is working on a different type of stem cell, multipotent adult progenitor cells (MAPCs), derived from adult bone marrow, to calm the immune response caused by ARDS.
Like MSCs, MAPCs attract less hostile attention from the immune system than other cell types. They do not have the distinctive molecular structures — the antigens — on their surface that typically induce a strong immune response, so they are less likely to cause a cytokine storm.
Eric Jenkins, senior medical director and head of clinical operations at Athersys, says one of the advantages of MAPCs over MSCs is that they can be multiplied in much greater volume in the lab. This provides a level of consistency that will help win regulatory approval.
“Being able to create millions of doses from a single donor collection permits you to develop a really well characterised, standardised and stable product on a commercial scale,” he says. “Having to frequently collect and culture bone marrow is problematic, because essentially it is a new product every time.”
Athersys already has an investigational MAPC product, MultiStem, which is used in late-stage clinical trials for acute ischemic stroke, and for ARDS in pneumonia patients. The US Food and Drug Administration has granted authorisation for MultiStem to be tested on Covid-19 patients with ARDS, and recruitment is under way. Other companies working on cell therapies for ARDS include Israel-based Pluristem, and Mesoblast, headquartered in Australia.
Mr Barker says a potential problem with damping down the immune response, which is what these cells do, is that it might enable the virus to proliferate more aggressively. “So perhaps you would only initially use it in patients who had developed severe lung disease,” he says.
Latest coronavirus news
Follow FT’s live coverage and analysis of the global pandemic and the rapidly evolving economic crisis here.
An alternative area of cell therapy for Covid-19 aims to strengthen the immune response early on by boosting the body’s “natural killer” (NK) cells, Mr Barker says. These are a type of white blood cell that attempts to contain viral infections. Caution is required, however. “Boosting NK cells might be useful, but data also suggest they can cause lung damage if they persist in the lungs for too long,” he warns.
What goes for treatments applies even more so for vaccines, which could be administered to millions of people.
“The safety profile has to be really skewed in your favour,” Mr Barker says. “The only thing worse than a vaccine that doesn’t work is a vaccine that hurts people.”