Could nanobodies from alpacas help CAR T-cell therapy to solid tumours?

An image of alpacas, whose nanobodies may help to treat solid tumours

Can nanobodies created from alpacas solve a problem in cancer treatment, by helping to treat solid tumours with CAR T-cell therapy?

Boston Children’s Hospital and MIT have shown that mini-antibodies, shrunk further to create nanobodies, could help to make CAR T-cell therapies work in solid tumours.

Hidde Ploegh, PhD, an immunologist in the Program in Cellular and Molecular Medicine at Boston Children’s and senior investigator on the PNAS study, said: “Our lab and the Hynes lab are among the few actively pursuing this approach of targeting the tumour micro-environment. Most labs are looking for tumour-specific antigens.”

Nanobodies from alpacas

In 1989, two undergraduate students at the Free University of Brussels found a previously unknown kind of antibody when testing frozen blood serum from camels. It was a miniature version of a human antibody which was made up of two heavy protein chains instead of two light and two heavy chains. The presence of these has since been confirmed in llamas and alpacas, which is how the team have been able to study nanobodies in alpacas.

Bryson and Sanchez, two alpacas who produce unusually small antibodies. These ‘nanobodies’ could help highly promising CAR T-cell therapies kill solid tumors, where right now they work only in blood cancers.
©Courtesy of Boston Children’s Hospital

CAR T-Cell therapy

CAR T-cell therapy is promising for blood cancers, and genetically engineers a patient’s T cells to make them better at attacking cancer. However, CAR T cells are not very successful at eliminating solid tumours, which is where nanobodies could help.

How they could be used in solid tumours

Ploegh explained: “Nanobodies could potentially carry a cytokine to boost the immune response to the tumour, toxic molecules that kill tumour and radioisotopes to irradiate the tumour at close range. CAR T cells are the battering ram that would come in to open the door; the other elements would finish the job. In theory, you could equip a single T cell with multiple chimeric antigen receptors and achieve even more precision. That’s something we would like to pursue.”

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