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Nanobodies to detect and target tumors

May 15, 2019

Researchers develop nanosized antibodies that home in on the meshwork of proteins surrounding cancer cells.

MAY 15, 2019, New York—Researchers led by Richard Hynes, the Daniel K. Ludwig Professor for Cancer Research at MIT, report in the current issue of the Proceedings of the National Academy of Sciences a new approach to detecting and treating tumors that targets not the cancer cells themselves but their surroundings.

The approach focuses on the extracellular matrix (ECM), a meshwork of proteins surrounding both normal and cancerous cells. The researchers found certain proteins that are abundant in regions surrounding tumors but absent from healthy tissues. Unlike the tumor cells themselves, these ECM proteins do not mutate as the cancer progresses, making them reliable markers for the presence of a tumor.

“Targeting the ECM offers a better way to attack metastases than trying to prevent the tumor cells themselves from spreading in the first place because they have usually already done that by the time the patient comes into the clinic,” said Hynes, who is also a member of the Koch Institute for Integrative Cancer Research at MIT.

The researchers developed a library of immune reagents designed to specifically target these ECM proteins, based on relatively tiny antibodies, or “nanobodies,” which are produced by alpacas. Because they are much smaller than antibodies, nanobodies can penetrate more deeply into human tissue and are cleared more quickly from the circulation following treatment.

The researchers demonstrated the effectiveness of their technique using a nanobody that targets a protein fragment called EIIIB, which is prevalent in many tumor ECMs. When they injected nanobodies tagged with radioisotopes into mice with cancer, and scanned the mice using noninvasive PET/CT imaging, a standard clinical technique, they found that the tumors and metastases were clearly visible.

The approach could also be used for therapy,” said Hynes. “We can couple almost anything we want to the nanobodies, including drugs, toxins or higher energy isotopes.”

In a recent collaborative paper, also published in Proceedings of the National Academy of Sciences, the researchers demonstrated the effectiveness of the technique by using it to develop nanobody-based chimeric antigen receptor (CAR) T cells designed to target solid tumors.

The MIT release from which this summary is derived can be found here.