ISCT’s New Leader on the Future of Cell and Gene Therapy – The Medicine Maker

In the early nineties, Jacques Galipeau was outside his native Canada, training at the Tufts New England Medical Center in Boston. It was an exciting time to be a young hematologist. The dream of gene therapy was becoming a reality, and with it came the promise of potential cures for the likes of sickle cell disease and thalassemia.

Fast forward, and we find a man who has ascended to lofty heights. At the recent 2022 meeting of the International Society for Cell & Gene Therapy, Galipeau was crowned as its new president. Here, we quiz Galipeau about the present and future of advanced medicine.

Well, the field has matured since the early nineties. Its worth remembering that the proof-of-concept for applying cell and gene therapies in humans arrived more than 30 years ago. Now, we have approved products! The first live cell vaccine approved by the FDA was Provenge in 2010. More recently, weve had the whole CAR T story, and in Europe weve seen the approval of mesenchymal cells for Crohns-related skin complications. All in all, its a very nice buffet.

As Im university based, my work is in discovery understanding how cells tick and how to make a better mousetrap out of them. We also work more boldly, testing first-in-human studies that may grow legs and march toward further development. At the University of Wisconsin-Madison, we have a special interest in virus-specific T cells and the version 2.0 of mesenchymal cells. As a scholar, these are my particular specialisms.

While wearing my ISCT hat, on the other hand, Im like a kid locked in a candy shop! There are so many exciting, emerging, and improved platforms, especially in immunotherapy and regenerative medicine. For some, the latter term is a dirty word because it has so often been bandied about as a catch-all everything for everybody. But now, were hearing about ongoing works like the clinical trials of induced pluripotent stem (IPS) cell-derived dopaminergic neurons for Parkinson's disease an excellent example of a highly promising regenerative medicine.

Regenerative medicines are replacement therapies, but the definition has now broadened to include all somatic cell therapies. Historically, regenerative medicine was all about stem cells, but more recently we have realized that there are many cells and tissues that can be used as living therapeutics, while having nothing to do with stem cells. For example, lymphoid cells and live tumor cell vaccines.

Absolutely. We humans are gregarious simians. Chimps dont talk its all nonverbal. Humans deal in a great deal of nonverbal communication too, and that cant be replicated online. So much of the spontaneity and exchange is leached away through the virtual interface. Not to mention the drop in dopamine levels!

Offline serendipity cant be replicated either. Everybody has a story that proves it. You turn and say hello to the person behind you in a queue for lunch at an event, and the next thing you know youre launching a collaboration. That doesnt happen on Zoom, where everyone is just one rectangle in a grid of video feeds.

It was a bold bet. Between our CEO Queenie Jang, our outgoing president Bruce Levine, and myself, we knew that we would have to make the call by October 2021. Reading the signs, we made plans for an in person event, and the result was a smashing success the biggest turnout weve ever had at an international meeting. I also think it helped prove that in-person events should remain the gold standard, with virtual hybridity as a bonus that remains well worth considering. Recording events is another pandemic practice wed like to keep alive. Having those recordings for future reference and wider access is really valuable. We want these international events to be absolutely optimal because they only come once per year and attending them isnt cheap especially for our friends flying in from afar!

We all know workforce development is an emerging topic, but I was surprised by just how strong the appetite for and imperative from stakeholders was. Had I not attended in person, I never would have got that impression.

From the perspective of platforms, I was surprised by the explosion of clinical-stage startups in cancer immunotherapy. Back in old school advanced therapy, the only way you could modify immune effector cells was using retroviral vectors. But now, we are seeing an explosion of emerging disruptive platforms that could be game changers as far as nimbleness is concerned.

Our societys focus on translational manufacturing, regulations, and first-in-human trials really sets us apart. In those areas, the technologists working in the field are really important. Theres a whole army of them. Thats why, at ISCT this year, we had a day for the technologists Saturday, to be precise.

It was standing room only! And it was great to see such a real uptick in attendance from people who are in neither business nor science. These are the people who really do the up-close work, and we learned that they have a real hunger for networking, change, and best practices. The ISCT is a knowledge-transfer organization, so we are more than happy to sate these appetites.

Last of all, Ill mention the real explosion of interest in exosomes as a therapeutic modality. Its lending a second life to the already popular interest in mesenchymal cells. Depending on how you tickle them in the petri dish, they spit out exosomes through which many of their functional attributes are transferred to tissues. This is a brand new development that is taking off in parallel with cancer immunotherapy, replacement therapy, and IPS.

I think the answer will be woven from different strands. In the case of established, approved, effective approaches that rinse, wash, and repeat 1000 times in a row, automation is your most obvious ally. But when youre still carrying out investigational development when youre building the plane as you fly it you may need some hands! Lab work can be a science in the same way cooking is a science. You need tactility, and more than a little artistry.

You really cannot underestimate the importance of having hands and being human! Take the analogy of baking a chocolate cake. I might give the exact same recipe to Bob and to Bert. Bob makes a beautiful cake, and Bert makes a burnt mess. Good hands and good instincts; some people have them, and some people just dont.

Compounding that, so many of our platforms are not set in stone. Disruptive technologies are loose in this field, and the task of incorporating and optimizing them is a hands-on affair. And thats where the workforce comes in. ISCT pays a great deal of attention here because we excel as a knowledge transfer and networking organization. Were not a university we cant confer diplomas but the way we pass on best practices and knowhow does make us serve as a sort of cooking school, if I may stretch my chocolate cake metaphor a little further.

We bring in domain experts that understand the obstacles and the friction points, and introduce them to newbies people who may well be very clever and have excellent degrees, but who still need to learn the ropes, and how to avoid beginners mistakes. Of course, you cant stop after initiation. This is an ever-evolving field of ever-evolving platforms. Penning a curriculum is not much use because it will likely be out of date by the time youve completed the first draft.

At ISCT events, we dont try to operate as a substitute for universities or technical colleges, as thats not our remit. Rather than disseminating knowledge through lecturing, we use a roundtable format. We set up a panel of experts, sit them down together, and let the audience listen to their back-and-forth in real time. Its an extremely valuable way to educate people on topics that wont appear in print for another year. In short, our attendees walk away as slightly more developed and informed professionals.

Right now, everybody is focusing on the highly impactful cell therapeutic platforms that have met marketing approval and are now commercially deployed. This is especially true in the case of cancer immunotherapy space, and even for Takedas mesenchymal product, Alofisel. The challenges here really hinge on the different regulatory environments that shape them.

In Europe, deployment and commercial success is dictated predominantly by universal payers and national entities. The US will be more of a wild west as far as pricing and reimbursement are concerned. I have no magic solutions for my commercial friends, but I do aim to help them understand the best practices that can ensure both ROI, as well as the sustainability and deployability necessary for distributive justice. Balancing ROI and access is not just a moral question; if one overtakes the other, the platform may collapse. Over time, competition ought to bring the current prices down. As more products are rolled out and sorted according to their effectiveness, potency, and ability to improve human outcomes, it is my hope and expectation that they will position themselves in a sustainable manner.

That said, I am currently very interested in another aspect that complements pharmas traditional central manufacturing, hub-and-spoke model: the democratization of advanced cell therapy, manufacture, and deployment. Bone marrow transplants serve as a good example. These are cell therapies, but since regulation does not define them as an advanced cell therapy, they do not require oversight by the EMA or FDA. Everything from cell collection and manipulation to re-administration is carried out in academic health centers. Industry had no direct involvement in the development of bone marrow transplants.

Now, with the explosion of cell therapies, the relevant technologies are becoming increasingly simple, and the prices are ever more robust. It is becoming easier to imagine that hospitals and other places of care could serve as a complement to large-scale manufacturing, especially for autologous cell therapies or one patient/one donor paradigms. There's a lot of new money in this space geared toward not only the traditional model, but also these complementary models of deployment. Thats something I think we need to face, as the future comes knocking.

Originally posted here:
ISCT's New Leader on the Future of Cell and Gene Therapy - The Medicine Maker