I’d like to summarize some things that I’ve read recently and that I’ve heard at the International Society for Cellular Therapy annual meeting , which finished last week. I see my mission right now in filling the gaps – between academic science and clinical medicine and between clinical medicine and business. And it is completely overlapping with ISCT’s mission – translation!
Cell therapy is very different from all other therapies that we have today. It frequently means an injection of live cells and has a potential to deliver a cure, not just control the symptoms. Unfortunately cell therapy has a lot of roadblocks on the way to clinical mainstream, much more than other therapeutics.
1. Risks and toxicity
There are a few issues here. Cell therapy treatment could be more risky or toxic for the patients only because they are frequently enrolled in trials after resistance to all other available therapeutics (pharmaceuticals and biologics). So patients coming to trials already tried everything else before and cell therapy is the last hope. Of course, in this case, the diseases are in very severe stages and patients could already suffer from toxicity of previous treatment. In these kind of settings it’s very hard to prove cell therapy efficacy. But if it works, the potential of this therapy is underestimated.
Another problem here is “trading safety for effectiveness”. For example, it’s a big question what degree of conditioning regimen should we apply in treatment of autoimmune diseases by hematopoietic stem cell (HSC) transplantation. Unlike cancer, where myeloablative conditioning is usual in order to replace “sick marrow” and achieve efficacy, autoimmune diseases are less fatal and frequently can be managed by drugs. And it’s very very hard to find “how much should we kill marrow” (degree of toxicity) in order to make transplanted cells work.
Richard Burt mentioned , that in earlier cell therapy trials for multiple sclerosis, he enrolled patients with different stages of disease, different pre-existing therapy and applied myeloablative conditioning. Such cell therapy appeared to be very toxic with mixed and hard to interpret results. In his recent trial – MIST  he enrolled a very narrow cohort of patients with multiple sclerosis.
So it is clear right now that cell therapy is not a panacea and going to work only in some cohorts of patients with chronic disorders.
2. Some cell therapy clinical trials were shut down simply because the sponsor ran out of money
Warren Sherman  mentioned that at least 2 phase III trials in Europe and US that assessed efficacy of cell therapy for cardiac repair were shut down, because the sponsor ran out of money. It is very sad, because average time for complete trial is 5-7 years in US. Now we need to patiently wait for results from other trials to get the answer. Small RegenMed companies simply have not enough money for phase III trials. Another example – HSC transplantation for treatment of autoimmune diseases:
Roadblocks include paltry funding – the trials lack commercial support because they’re not testing new drugs – and difficulty finding patients, because rheumatologists and neurologists are skeptical of transplants, and new, promising, and generally safer biologic therapies are competing for patients’ attention.
I don’t think this problem is specific for cell therapy, but it’s really affecting the field.
3. Lack of enrollment in cell therapy trials
Some cell therapy clinical trials are really affected by lack of participants, because many physicians remain skeptical and don’t refer patients. One of the good examples here, again – HSC transplantation for autoimmune diseases.
One of the biggest challenges has been finding patients. A European trial for MS closed in December after recruiting just 21 people out of the once-hoped-for 200. In pediatrics, Woolfrey and her colleague Carol Wallace, at Seattle Children’s Hospital, have sought patients for more than 5 years for a trial in pediatric autoimmune disease and transplanted only four, all with juvenile arthritis.
On the other hand, if treatment is still considered as experimental but not mainstream, insurance companies are not willing to cover such procedures:
In the United States, insurance companies often decline to pay for the transplants, deeming them too experimental, thereby limiting trial enrollment; commercial funding is not an option because new drugs are not being tested. In Europe, government restrictions often control how many transplants can be performed at a given site. At University Medical Center Utrecht in the Netherlands, for example, national insurance companies will pay for about 35 stem cell transplants a year, says Nico Wulffraat, a pediatric rheumatologist at the hospital. Most of those go to cancer patients.
To minimize risks and toxicity, mentioned above, enrollment criteria should be very stringent. This narrowing of enrollment criteria also could contribute to lack of patients.
Because cell therapy is very different from all other existing therapies that we have right now, it should be regulated differently. How to regulate cell therapies is a really tough question. Regulatory agencies can not simply apply all the same rules as they have for pharmaceuticals and biotech products. Even within cell therapy regulation could be different depending on cell source (autologous or allogeneic) or degree of cell manipulations ex vivo (few hours processing or 1-3 months of culture). Because in many cases regulatory agencies have to make new rules from scratch, it could take some time to complete.
5. Widespread bogus stem cell tourism can discredit cell therapy
I’ve written about so-called “stem cell tourism” before, and indicate that one of the problems could be loss of trust to the field from public and from professional communities (physicians). This kind of mistrust can cause lack of fundings and public support.
Despite all of these roadblocks cell therapy trials continue and many of the results are very encouraging. I believe that a significant part of the few hundred trials currently going on around the world will work and some of them will become mainstream clinical medicine.
all citations from: Couzin-Frankel J. Immunology. Replacing an immune system gone haywire. Science. 2010 Feb 12;327(5967):772-4