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Synthetic protein takes BiTE out of brain tumors

Bispecific antibodies stick immune cells to cancer cells like Velcro
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Engineered to link with T cells on one side, and a cancer cell on the other, the BiTE serves as a connector that tethers cancer to its killer.--Courtesy of Duke Medicine

A team of researchers at Duke University Medical Center has created a synthetic protein, known as a BiTE (bispecific T-cell engager) that hooks together brain tumor cells and immune cells, like Velcro. This redirects the immune response to kill the cancer cells without affecting healthy cells.

One end of the molecule is tagged with a fragment of an antibody against a mutated form of the growth factor receptor, EGFRvIII. The antigen EGFRvIII appears on the surface of glioblastoma and other cancer cells but not on healthy cells. The other end has an antibody fragment that recruits T cells, and this specificity should cut the side effects seen in previous attempts. This triggers an immune response against the tumor.

Glioblastomas are tough cancers to treat. They are universally fatal with survival measured in months. This treatment can cross the blood-brain barrier, getting right to the site of the tumors. When mice with brain tumors were treated with the two-armed protein, it localized to the tumor and 6 of the 8 animals were cured, even with bulky and invasive cancers.

"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 Sampson, a neurosurgeon at The Preston Robert Tisch Brain Tumor Center at Duke in Durham, NC.

The next step is to see if the treatment can be used alongside existing treatments such as radiotherapy and chemotherapy.

- read the press release
- see the abstract

Special Reports: 10 Next-Gen Biologics PlatformsMicromet: BiTES | MacroGenics: DARTs

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