Nav: Home

T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma

January 16, 2018

WASHINGTON-(Jan. 16, 2018)-Tumors have come up with ingenious strategies that enable them to evade detection and destruction by the immune system. So, a research team that includes Children's National Health System clinician-researchers has validated a way to outfox the tumors. They engineered T-cells, essential players in the body's own immune system, to strip tumors of their self-preservation skill and were able to hold Hodgkin lymphoma at bay in patients with relapsed disease for more than four years. What's more, they infused patients with the tumor-directed T-cells without requiring "pretreatment" chemotherapy.

Results of the small study were published online Jan. 9, 2018, in the Journal of Clinical Oncology.

"These results come 18 years after this revolutionary approach was first conceptualized. While the study is small, its findings are incredibly encouraging for our families and for the cancer field," says Catherine "Cath" M. Bollard, M.D., M.B.Ch.B., director of the Children's Research Institute's Center for Cancer & Immunology Research and lead study author.

"I started work in this area in 2000," says Dr. Bollard. "At that time, the oncology community had little enthusiasm for the use of T-cell therapies to treat cancer. Even then, when T-cell therapy was in its relative infancy, some research institutions began to see more than 90 percent complete responses and cure rates in some settings. This most recent study points to the potential of specialized T-cells to fight even more types of immune-evading tumors."

T-cells seek out and destroy proteins expressed by cancer cells or virus-infected cells, protecting the body from infection and malignancy.

In the dose-escalation study, eight patients with Epstein Barr virus-positive Hodgkin lymphoma received as few as 2 and as many as 12 doses of between 2 × 107 and 1.5 × 108 cells/m2 of specially engineered T-cells. Production of transforming growth factor-β in the immediate vicinity of tumors thwarts tumor-directed therapies by having devastating effects on T-cell function in vivo.

So, the research team forced expression of a dominant-negative TGF-β receptor type 2 (DNRII) onto LMP-specific T-cells (DNRII-LSTs) that were specially designed to seek out and destroy proteins derived from the Epstein Barr virus expressed by the tumor cells. The DNRII expressed by the T-cells allowed the cells to resist the hostile tumor environment and seek out and kill the tumor cells. Seven of the eight patients treated had active disease at the time of T-cell infusion.

"DNRII-LSTs were resistant to otherwise inhibitory concentrations of TGF-β in vitro and retained their ability to kill the cancer cells. After infusion, the signal from the genetically modified T-cells in the peripheral blood increased up to 100-fold," writes Dr. Bollard and colleagues, adding that "DNRII-LSTs persisted for up to four years. Four of the seven patients with active disease achieved clinical responses that were complete and ongoing in two patients for more than four years, including in one patient who achieved only a partial response to unmodified tumor-directed T-cells."

The study team writes that their findings underscore the potential utility of expressing DNRII when battling other tumors that have learned to evade the immune system.
-end-
Study co-authors include Conrad Russell Y. Cruz, M.D., Ph.D., and Cecilia Barese, M.D., Ph.D., Children's National; Gianpietro Dotti, UNC; Stephen Gottschalk, St. Jude Children's Research Hospital; Tamara Tripic, Vicky Torrano, Olga Dakhova, George Carrum, Carlos Almeida Ramos, Hao Liu, Meng Fen Wu, Andrea N. Marcogliese, Adrian P. Gee, Malcolm K. Brenner, Helen E. Heslop and Cliona M. Rooney, study senior author, Baylor College of Medicine; Youli Zu and Daniel Y. Lee, Houston Methodist; and Owen A. O'Connor, Columbia University Medical Center.

Children's National Health System

Related Immune System Articles:

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.
Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.
COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.
Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.
Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.
Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.
Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.
How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.
Immune system upgrade
Theoretically, our immune system could detect and kill cancer cells.
Using the immune system as a defence against cancer
Research published today in the British Journal of Cancer has found that a naturally occurring molecule and a component of the immune system that can successfully target and kill cancer cells, can also encourage immunity against cancer resurgence.
More Immune System News and Immune System Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.