Science Daily reported on 11 April that investigators are using unusually small antibodies made naturally by alpacas, camels and llamas to target the environment around tumours in a new approach to developing CAR-T therapy for solid tumours.
Researchers at Boston Children’s Hospital and MIT have shown that these ‘mini-bodies’ can successfully curb melanoma and colon cancer.
One of the greatest challenges in producing effective CAR-T therapy for treating solid tumours is to negotiate the extracellular matrix that surrounds and protects solid tumours from immune attack. The immune system needs to overcome this barrier as well as immunosuppressive molecules that weaken T cell attack.
In 1989 two undergrad students at the Free University of Brussels stumbled across a previously unknown kind of antibody in frozen blood serum from camels. The antibody was a miniature version of a human antibody and its presence was eventually reported in llamas and alpacas.
The Boston Children’s/MIT researchers’ work was published in PNAS this week and show that these mini-antibodies, which were shrunk further to created ‘nanobodies’, might go some way to addressing the problem of overcoming the immunosuppressive nature of the tumour microenvironment. The research team, led by senior investigator Hide Ploegh, PhD, have harnessed the nanobodies to carry imaging agents, allowing for precise visualisation of metastatic cancers.
“A lot of people got into the game and began to appreciate nanobodies’ unique properties,” he says.
Researchers tested the nano bodies in two separate melanoma mouse models as well as a colon adenocarcinoma mouse model. The nanobody-based CAR-T cells killed tumour cells, significantly slowed tumour growth and improved the animals’ survival, with no apparent side effects.
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