What’s New in Cell Therapy Research and Treatment?
Summary
- The world’s foremost hematology researchers met in San Diego at the American Society for Hematology’s annual meeting in December.
- Sylvester’s Damian Green, M.D., shared his reflections on new findings and trends in cell therapy for blood cancers.
- As chief, Dr. Green’s plan for the Division of Transplantation and Cellular Therapy is to create more effective cellular therapy with fewer side effects.
Growing up, Damian Green, M.D., was the kid who would run to grab the first aid kit when someone was injured.
“From the earliest age I can remember, I was very motivated to try and help people if they were hurt or injured,” said Dr. Green, the Ron and Nedra Kalish Family Endowed Chair in Stem Cell Transplantation and professor of medicine and chief of the Division of Transplantation and Cellular Therapy at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine.
His father was also a doctor — a hematopathologist — and early experiences looking at blood slides through a microscope together drove Dr. Green to pursue a career in medicine. When he first started treating blood cancer patients, he realized that they didn’t have the luxury of time. As such, they are often open to new treatments and more willing to participate in clinical research.
“I remember some of the early cancer patients I cared for and how remarkably willing they were to help others, even if they weren’t going to benefit directly,” Dr. Green said. “Their altruism was very motivating for me.”
What is Cellular Therapy?
Working to help these patients brought Dr. Green to study experimental treatments. Now, he’s saving lives by developing and improving next-generation cancer treatments called cellular therapies.
Cellular therapy is the use of living cells to treat or cure diseases. It typically involves introducing, modifying or stimulating cells in or from a patient’s body to repair damaged tissue, fight diseases or restore normal function.
Often, these cellular therapies involve training a patient’s white blood cells to fight cancer. Doctors do this by removing the white blood cells from the body, making genetic changes and putting them back in the patient.
“We’re still in the relatively early days. It takes a long time to refine these forms of therapy,” Dr. Green said. “They are already incredibly potent, and yet there’s much we can do to improve them further to see less toxicity and better outcomes.”
Dr. Green’s specialty is blood cancers, and he recently joined the world’s foremost hematology researchers in San Diego at the 66th annual American Society for Hematology’s (ASH) meeting.
Following the ASH 2024 meeting, Dr. Green shared his reflections on several exciting trends in cell therapy. These trends highlight a growing emphasis on expanding applications, improving safety and personalizing treatment to improve outcomes, topics Dr. Green and other Sylvester researchers are also studying.
Expanded Uses of Cellular Therapy
Currently, cellular therapies are primarily used for blood cancers. But there is potential for broader applications, Dr. Green said. These include solid cancers, cancer-associated diseases like amyloid light-chain amyloidosis and non-cancer autoimmune disorders.
Preliminary studies presented at ASH and by Sylvester researchers have shown strong responses in some of these trials.
“We here at Sylvester are also looking at how cell therapy can be used to treat patients with autoimmune disease,” Dr. Green said. “We may be able to harness the power of the cell therapy to treat lupus, for example.”
He’s also focused on extending these treatments to other blood cancers, particularly acute myeloid leukemia (AML).
“It’s tough to develop a cellular therapy for AML,” Dr. Green said, “but these patients need better options.”
Why Some Cellular Therapies Fail
One of the hurdles of cellular therapy is that it can cure some conditions, like acute lymphoblastic leukemia or lymphoma, but patients with other cancers, like multiple myeloma, almost always have their disease come back.
“One of the major areas of focus — ours, across the country and worldwide — has been understanding relapse so that we can figure out what to do differently to prevent it,” Dr. Green said.
Some cellular therapies may be prone to relapse because the modified white blood cells die off or become less effective over time. One potential way around this is to use gene-editing technologies on a patient’s own cells without removing them from the patient’s body.
These would create “in vivo generators,” which could allow ongoing replenishment of modified T cells over time. This approach may enable long-term, sustainable treatment.
“In vivo CAR-T production is in its infancy, but it’s an area of great excitement,” Dr. Green said.
More Effective Options With Fewer Side Effects
Understanding relapse also involves studying factors that influence the immune system before cell therapy starts. One central question is whether prior treatments, like chemotherapy or radiation, have lasting effects on T-cell function. This could negatively affect cellular therapy outcomes.
A way to avoid the effects of toxic prior treatments is to use these cellular therapies earlier, when they may prove to be more effective. This allows doctors to harness the patient’s immune system while it’s healthier — before it’s exhausted by disease, opportunistic infections and other therapies.
For instance, the FDA has recently expanded access to cellular therapy for multiple myeloma after one or two failed therapies. Researchers are even studying cellular therapies for high-risk pre-cancerous conditions.
The problem with using these therapies early in a disease course is that they can have side effects. So, another major focus area is improving cellular therapy’s toxicity and side-effect profiles. Severe side effects include infections and neurologic complications. Newer cellular therapies presented at ASH showed better safety profiles and excellent outcomes.
One way to mitigate toxicities is to combine therapies. Some new cell therapies target multiple antigens simultaneously, while others combine cellular therapy and other treatments.
“If the tumor is evading one approach, you can hit it from another angle and hope it can’t evade both,” Dr. Green said.
Sylvester researchers have been pursuing many of these areas of innovation. When expanding the Division of Transplantation and Cellular Therapy, they are at the top of Dr. Green’s mind. Sylvester researchers are working to improve cellular therapies, apply them to other diseases and create combination strategies.
“We are shedding light to advance cell therapy discoveries, and it is fitting that bright rays of hope emanate from Miami,” Dr. Green said.
Tags: Acute Myeloid Leukemia, cancer research, CAR T cells, Division of Cellular Therapy and Transplantation, Dr. Damian Green, gene editing, Sylvester Comprehensive Cancer Center