Cancer cells fool our immune system by hijacking the mechanisms that immune cells use to recognize friends from foe. Scientists are learning to overcome this strategy with drugs called immune checkpoint blockade (ICB), which interfere with the contact between immune cells and cancer cells and make the latter recognisable as enemies. This is revolutionising treatments, especially for melanoma, a type of skin cancer. But in half of patients, this therapy does not prevent cancerous cells from escaping surveillance and proliferating freely. Now, an international research team led by Maria Rescigno at the Humanitas Research Hospital in Milan has found a few peptides (a sort of shorter and simplified version of proteins) that could be used as an anticancer vaccine, and combined with ICBs to prevent metastasis in the patients who would not respond otherwise.
Having to survive and proliferate in a hostile environment, cancerous cells have their own mechanisms to respond to stress. The scientists played with that stress by infecting mouse melanoma cells with Salmonella typhi, a bacterium that infects the intestine and the blood, causing typhoid fever. They collected the molecules secreted by the infected cells, they injected them in mice, and a few weeks later they injected again the mice with melanoma cells. As a result, the vaccinated mice were indeed more protected from tumour growth than an untreated control group.
The scientists then tried the same procedure on a few dogs affected by osteosarcoma, a similar type of tumour. They took tumour cells from the animals, cultured them and infected them with Salmonella, collected their secretome (all the substances they released in the extracellular space) and used it as a vaccine. All the treated dogs had a benefit in terms of survival and metastasis.
As a further step towards the application in humans, the scientists finally infected several different cultures of human melanoma cells with the bacterium, analysed their secretomes, and isolated 12 peptides that activate human immune cells. These peptides seem to be produced by all melanoma cells in all patients – but not by healthy skin cells – when infected. Should efficacy be confirmed, this cocktail of peptides could be used right after surgery, to prime the immune system to clear the body from micro-metastases that often are not clinically visible. “Our results pave the way for a shared vaccination strategy against metastatic disease in humans, but also for better cures for dogs”, says Alessia Melacarne, first author of the article published in Cell Reports1.
“The finding provides a novel tool, and may have a significant impact in the cancer immunotherapy field in a medium-long term” says Luigi Buonaguro, director at the National Cancer Institute-IRCCS ‘Pascale’ in Naples, who was not involved in the study.
Melacarne A, Ferrari V, Tiraboschi L et al., Cell Rep. 36 (2021).