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Senior Lab Specialists Joseph Burkholder and Kreg Grindle in the UW Health Clinical Hematopoietic Cell Therapy Lab, culturing a patient’s dendritic cells during manufacturing of a AML-dendritic cell fusion vaccine.
Cellular therapy – the idea that you can transplant new, healthy cells into a patient’s body – has long been an appealing option for medical scientists and researchers seeking ways of treating various ailments. But it was here at UW-Madison where cell therapy was proven as a viable option for treating cancer.
In the 1960s, physician-scientist Fritz Bach, MD, developed a compatibility test between organ donors and recipients, which enabled him to lead one of the world's first successful matched bone marrow transplants in 1968.
Now, bone marrow and stem cell transplants have become key treatments for many different forms of hematologic cancers, such as leukemia, lymphoma and multiple myeloma. Since being established in 1981, the UW Blood and Marrow Transplant (BMT) program has cared for thousands of patients, either receiving a transplant or donating their own marrow or stem cells.
Cell therapy research, meanwhile, continues to evolve in new and exciting ways at the UW Carbone Cancer Center.
Peiman Hematti, MD, is the director of Clinical Hematopoietic Cell Processing Laboratory at UW-Madison. Much of his research is aimed at improving post-transplant immunological complications, such as graft-versus-host disease. But Hematti and his team are also working to develop and test new cellular therapies for cancer treatment.
His lab’s ability to do that took a giant step forward in late 2020 when they received word from FACT – the Foundation for the Accreditation of Cellular Therapy – that the lab had received certification to do “more than minimal cell manipulation.”
“This is a big deal,” Hematti said. “We are the only lab on campus that has this accreditation, which is the culmination of years of working hard and proving that we can do it right and credit goes to our entire team and especially our senior cell therapy lab specialists.”
Simply collecting a patient’s bone marrow or stem cells, freezing and later thawing them, and infusing them into another patient who needs them is an example of minimal manipulation. Cells essentially come out and go in with minimal processing in between, which does not change the biological make-up of the cells.
But making any significant changes to those cells over a period of time is considered more than minimal manipulation. And it turns out there’s good reason to do this.
“With a stem cell product, for example, you can do things such as culture expansion,” Hematti said. “You can actually change the biology of these cells over time, and then re-introduce them to a patient, which opens up new possibilities to fight cancer.”
It’s a great power, but also a great responsibility. Giving a patient more than minimally manipulated cells can stimulate incredible immune responses, but can also cause severe consequences if done incorrectly. That’s why more than minimal cell manipulation is highly-regulated by the FDA, and getting FACT accreditation to do it is no easy feat.
However, the lab recently showed they were more than up to the task. Because of an expertise in cell processing, UW was selected as a partner in a national clinical trial that tested the effectiveness of a personalized myeloma cellular vaccine. Unlike a traditional vaccine, which is preventative, a cancer vaccine seeks to fight an existing threat in the body using the patient’s own cells, processed in a lab, to stimulate a specific immune response.
In this study, led by Natalie Callander, MD, cancerous bone marrow and healthy blood cells were taken from individual multiple myeloma patients, and cultured together in the lab for about two weeks. “We were able to fuse the cancer cells with the normal blood cells to create a cancer vaccine, which is essentially a new type of cell.” Hematti said. “We effectively changed the biology of the cells, which is the definition of more than minimally manipulated. And we were super successful with that clinical trial.”
That study not only paved the way for the recent FACT accreditation, but proved that UW could effectively and safely handle these types of novel cell therapy clinical trials.
Now, UW has been called upon again by primary investigators at Harvard, this time to test another personalized vaccine. The target this time around is acute myeloid leukemia or AML. The study, which is led by Aric Hall, MD, is currently recruiting patients and takes a similar approach to combining a patient’s dendritic cells and tumor cells to create a cellular vaccine.
Vaccine for the first patient in this study was just recently generated, and Hematti hopes more will soon be on the way. “AML is usually a very difficult disease to treat, and there are many times when we run out of options,” he said. “We believe this approach may offer AML patients a treatment option that could provide long term control of their disease, without receiving toxic chemotherapy. Having a cellular vaccine, if proven to be effective for this type of cancer, could be game changing.”
Outside of vaccine development, Hematti says the new accreditation opens up additional avenues for researchers to explore, including the in-house creation of CAR T-cells, which can be used to treat certain types of blood cancer. CAR T-cell therapy was first approved by the FDA in 2017 – thanks partially to testing at UW Carbone – and is being offered as a treatment to some patients.
Being able to create these cells in-house, as opposed to contracting with an outside lab, could mean that patients who need this treatment could receive it faster and with less manufacturing cost.
It’s easy to see why researchers are optimistic about what this could all mean for the future of cancer treatment. And during a year when many are looking for success stories – it’s the 50th anniversary of the National Cancer Act, after all – you don’t have to look much further than what’s happening in cell therapy.
“My goal here at UW has always been to bring innovative therapies to our patients and make sure that UW stays at the forefront of such cutting edge research,” Hematti said. “It’s exciting to think about where we can go next.”