Andrew Masterson
Andrew Masterson is a former editor of Cosmos.
A combination of a tiny segment of DNA and a specific antibody injected into a solid tumour has been shown to remove not only the target tumour, but also others in the body, at least in mice.
So confident are they of the effectiveness of their approach, scientists at the Stanford University School of Medicine in the US are this month starting a clinical trial using human patients.
Like several other treatments, the combination therapy, reported in the journal Science Translational Medicine, prompts the body’s own immune system to tackle tumours. However, unlike others, it functions as a one-size-fits-all strategy. To a significant extent, it seems, it is not necessary to first identify the type of cancer involved.
“When we use these two agents together, we see the elimination of tumours all over the body,” says oncologist Ronald Levy, one of the authors of the study.
“This approach bypasses the need to identify tumour-specific immune targets and doesn’t require wholesale activation of the immune system or customisation of a patient’s immune cells.”
The Stanford team’s strategy works by exploiting the curiously ambivalent relationship between cancer tumours and immune cells called T cells. The latter function to attack bodily invaders through detecting abnormal proteins.
Initially the T cells will recognise such proteins on the surface of cancer cells and enter the developing tumour. However, as the tumour continues to grow, T cell activity drops off. In a sense, the immune system gives up.
Levy and his colleagues found a way to reactivate the moribund T cells. To do this, they inject a target tumour with a couple of micrograms of a short stretch of DNA called a CpG oligonucleotide. This works with nearby immune cells to activate a receptor called OX40 on the surface of the T cells.
CpG oligonucleotide is already used to bolster several types of cancer treatment.
At this point, the second agent – an antibody that binds to OX40 – comes into action, revivifying T cells, but only those within the tumour. This is important, because the combination effectively generates a cohort of immune cells pre-programmed to attack only cancer-specific proteins.
Once the process is under way, the scientists report, the tumour-hungry T cells leave the initial site and distribute through the body, attacking any and all other similar tumours they find.
“Our approach uses a one-time application of very small amounts of two agents to stimulate the immune cells only within the tumour itself,” explains Levy.
“In the mice, we saw amazing, body-wide effects, including the elimination of tumours all over the animal.”
The therapy has been trialled against several different types of cancers in mice. The first trial involved 90 animals with lymphoma tumours on both sides of their bodies. In each, only one tumour was treated. The paper details that 87 out of the 90 were cured. The cancer returned in three cases, but went into permanent remission after a second treatment.
Mice carrying breast, colon and melanoma tumours were also treated successfully. Trials were also conducted on mice genetically engineered to develop multiple breast cancers. In many cases treating the first tumour to appear prevented others arising.
While the treatment is effective against a range of cancers, each application conditions T cells to fight only one. Tests on mice with two types of tumour found that only the type treated went into remission, leaving the other unaffected.
“This is a very targeted approach,” Levy says. “Only the tumour that shares the protein targets displayed by the treated site is affected. We’re attacking specific targets without having to identify exactly what proteins the T-cells are recognising.”
An initial human trial will get underway soon, with the researchers looking to recruit about 15 patients with low-grade lymphoma.
