New immune therapy treats brain tumors in mice

Engineered to specifically link with the body’s immune fighters (T-cells) on one side, and a cancer cell on the other, the bispecific T-cell engager (BiTE) serves as a connector that tethers cancer to its killer. Credit: Duke Medicine

Using an artificial protein that stimulates the body's natural immune system to fight cancer, a research team at Duke Medicine has engineered a lethal weapon that kills brain tumors in mice while sparing other tissue. If it can be shown to work in humans, it would overcome a major obstacle that has hampered the effectiveness of immune-based therapies.

The protein is manufactured with two arms – one that exclusively binds to tumor cells and another that snags the body's fighter T-cells, spurring an attack on the tumor. In six out of eight mice with , the treatment resulted in cures, according to findings published Dec. 17, 2012, in the .

"This work represents a revival of a somewhat old concept that targeting cancer with tumor-specific antigens may well be the most effective way to treat cancer without toxicity," said senior author John H. Sampson, M.D., PhD, a at The Preston Robert Tisch Brain Tumor Center at Duke. "But there have been problems with that approach, especially for brain tumors. Our is exciting, because it acts like Velcro to bind T-cells to and induces them to kill without any negative effects on surrounding normal tissues."

Sampson and colleagues focused on the immune approach in brain tumors, which are notoriously difficult to treat. Despite surgery, radiation and chemotherapy, are universally fatal, with a median survival of 15 months.

Immunotherapies, in which the body's B-cells and T-cells are triggered to attack tumors, have shown promise in treating brain and other cancers, but have been problematic in clinical use. Treatments have been difficult to administer at , or have spurred side effects in which the immune system also attacks healthy tissue and organs.

Working to overcome those pitfalls, the Duke-led researchers designed a kind of connector - an artificial protein called a bispecific T-cell engager, or BiTE – that tethers the tumor to its killer. Their newly engineered protein includes fractions of two separate antibodies, one that recruits and engages the body's fighter T-cells and one that expressly homes in on an antigen known as EGFRvIII, which only occurs in cancers.

Once connected via the new bispecific antibody, the T-cells recognize the tumor as an invader, and mount an attack. Normal tissue, which does not carry the tumor antigen, is left unscathed.

"One of the major advantages is that this therapy can be given intravenously, crossing the blood-brain barrier," said lead author Bryan Choi, a dual M.D-PhD candidate at Duke. "When we gave the therapy systemically to the mice, it successfully localized to the tumors, treating even bulky and invasive tumors in the central nervous system."

The team also developed an antidote to other current immune-targeting therapies that have a toxic effect, enhancing their safety profiles and bolstering their effectiveness.

"Additional studies will concentrate on whether these findings can be replicated in human trials, and whether the treatment is affected by the use of current therapies such as radiation and chemotherapy," Sampson said.

Related Stories

Targeted Immune Cells Shrink Tumors in Mice

Feb 10, 2009

(PhysOrg.com) -- Researchers have generated altered immune cells that are able to shrink, and in some cases eradicate, large tumors in mice. The immune cells target mesothelin, a protein that is highly expressed, or translated ...

Recommended for you

Study unlocks basis of key immune protein's two-faced role

Nov 26, 2014

A Brigham and Women's Hospital-led team has identified a long sought-after partner for a key immune protein, called TIM-3, that helps explain its two-faced role in the immune system—sometimes dampening it, other times stimulating ...

Profilin can induce severe food-allergic reactions

Nov 25, 2014

(HealthDay)—Profilins are complete food allergens in food-allergic patient populations that are exposed to high levels of grass pollen, according to a study published in the December issue of Allergy.

Structured education program beneficial for anaphylaxis

Nov 21, 2014

(HealthDay)—A structured education intervention improves knowledge and emergency management for patients at risk for anaphylaxis and their caregivers, according to a study published online Nov. 19 in Allergy.

User comments

Adjust slider to filter visible comments by rank

Display comments: newest first

wealthychef
5 / 5 (2) Dec 17, 2012
Wow, this sounds incredibly promising! I am not sure, but it sounds like this cured brain cancers in mice with zero side effects. Am I reading it correctly? Or does it just kill a few tumor cells?
Grallen
5 / 5 (1) Dec 18, 2012
You're reading it right. It just facilitated a normal immune response VS cancer.

The person will probably feel "sick" during the process. How sick would depend on how bad the cancer was and how fast they try to cure it.
elektron
3 / 5 (4) Dec 18, 2012
Should we really be doing research to save mice from brain tumours? I say, let them die.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.