4 minute read
health
Cancer’s Formidable Foe
OSU researchers take an innovative “triple threat” approach to cellular therapy
By Claire Miller
Photo courtesy of The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital
MORE AND MORE, research innovations are allowing us to tap into our own natural defenses to fight cancer.
Advances in immunotherapy, specifically cellular therapy, utilize lymphocytes, a subtype of white blood cells, that have functions of fighting infection, killing infected cells, and attacking and eliminating viruses.
Scientists are able to culture and modify patients’ own B lymphocytes (B cells), T lymphocytes (T cells) and natural killer cells to harness the power of the immune system against cancer, and it’s proven highly effective.
“I don’t have a problem calling it a revolution,” says Dr. Marcos J. de Lima, director of the Blood and Marrow Transplant and Cellular Therapy programs at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.
The Ohio State University was one of the first cancer hospitals in the U.S. to offer CAR-T therapy, the first cellular therapy for blood cancer, to patients in October 2017.
CAR stands for chimeric antigen receptors, which are proteins that are engineered on T lymphocyte cells to allow them to target and attack specific types of cancer cells.
There’s been great promise and even more promising results in CAR-T therapy. Two of the first patients to receive CAR-T therapy, at the University of Pennsylvania in Philadelphia, to treat their chronic lymphocytic leukemia in 2010 are still in remission, according to a study released in 2022.
The latest CAR-T therapy research happening at OSU uses a “triple threat” approach.
“What is innovative about it is this is the first in human attempt in targeting three cancer structures,” de Lima says.
Researchers have found that cancer cells learn to evade trained T lymphocyte cells that are targeting the biomarker CD19, so they eventually stop making the protein. To avoid the cancer’s escape tactics, the OSU study will use C19, CD21 and CD22 markers in its CAR-T therapy.
The James has treated its first patient with the new triple CAR-T therapy, and has treated 300 patients with CD19-only CAR-T therapy since 2017.
“The success of this endeavor is only measured by how many people we can treat,” de Lima says. “That should be the only metric that matters.”
The same science is also used for CARNK therapy using natural killer cells, another component of the blood that be harnessed to fight off cancer. CAR-T therapy has exciting applications outside of cancer as well.
De Lima’s department is working with collaborators outside of OSU to develop a CAR-T therapy against HIV.
“The idea is to create a T lymphocyte that targets cells infected with HIV, hoping that this will help towards an HIV cure,” he says. “The applications are endless.”
There’s also a genetic therapy for sickle cell anemia that could soon be on the market.
The therapy, called LentiGlobin, recently received preliminary approval from the FDA, meaning it could have commercial product available next year. The treatment reinfuses the patient’s own stem cells – which means no risk of rejection – into their blood to ultimately form new healthy red blood cells from their bone marrow.
Cellular Expansion
Due to the advances in research in the field, cancer treatment has been expanded to include cellular therapies, in addition to the long-standing treatments of surgery, radiation and chemotherapy. Over time, de Lima expects the role of immunotherapy to increase, while there will be less need to rely on traditional therapies.
De Lima has been tasked with expanding the cellular therapy program in his role at the James.
This includes finding ways to make processes faster and make therapies more accessible. For example, rather than using a commercial CAR-T product that requires collecting the T lymphocytes, shipping them to a centralized laboratory and then waiting for them to be returned as a frozen product several weeks later vastly increases efficiency.
“Our in-house manufacturer takes six days,” de Lima says. “The idea is obviously the faster we treat people, the less chemotherapy they need, right? In cancer treatment, time is measured in chemotherapy, unfortunately.”
In the future, developing local manufacturing may also decrease the price of the expensive therapies.
Another part of expansion is addressing the middle ground of the process it takes to go from scientific research to health care.
“OSU has exceeded traditionally in basic science and in care delivery,” de Lima says. “But if you think about it, these are two extremes of a process.”
OSU is willing to invest in the middle ground of moving from promising science in an animal model to what it takes to safely translate those results to patient trials.
Bridging the gap in the process requires investing in infrastructure for human trials and manufacturing, which in turn requires greater regulations and scrutiny than animal models. Infrastructure, de Lima says, includes brick-and-mortar elements, but also – and, arguably, most importantly – people. His department is now hiring more people and expanding internally.
“There’s no doubt that we depend on hero patients who are willing to participate in clinical trials. Let’s not forget that,” de Lima says. “These folks are all heroes. I think the main message in my opinion, from a human standpoint, is that this is very much a human enterprise, and don’t forget the patients.” CS
Claire Miller is an editor at CityScene Media Group. Feedback is welcome at cmiller@cityscenemediagroup.com.
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