Personalised cancer vaccines yield promising results
New approach involves mapping DNA of individual patients’ tumours
Revolutionary personalised cancer vaccines tailored to individual patients have produced highly promising results in an early clinical trial.
The vaccines against deadly melanoma skin cancer triggered a “very strong” immune response in three patients with no adverse side effects.
Crucially, the customised vaccines appeared to boost the number and diversity of immune system “killer T-cells” that target tumours.
Findings from the first three patients given the treatment are published in the journal Science.
Scientists believe they could pave the way to personalised immunotherapy not only for melanoma but also other cancers.
Trial leader Dr Gerald Linette, from Washington University School of Medicine in St Louis, US, said: “This proof-of-principle study shows that these custom-designed vaccines can elicit a very strong immune response.
“The tumour antigens (proteins) we inserted into the vaccines provoked a broad response among the immune system’s killer T-cells responsible for destroying tumours.
“Our results are preliminary, but we think the vaccines have therapeutic potential based on the breadth and remarkable diversity of the T-cell response.”
The Phase I trial was designed to evaluate safety immune response, not long-term effectiveness which will have to be assessed in future studies.
Previous cancer vaccines have focused on normal proteins commonly present at high levels in particular kinds of tumour. But those same proteins are also found in healthy cells, making it difficult to trigger a potent immune response.
The new approach involved first mapping the DNA of individual patients’ tumours and samples of healthy tissue to identify proteins unique to cancer cells.
Computer analysis and laboratory tests revealed which of these “neoantigens” would be most likely to stimulate a strong immune response and work in a vaccine.
Each of the melanoma patients had undergone surgery to remove their tumours but experienced cancer spread to the lymph nodes.
The Phase I trial, enrolling a total of six patients, was approved by the US medicines regulator, the Food and Drug Administration (FDA), as part of an investigational new drug application.
Co-author Dr Elaine Mardis, co-director of the McDonnell Genome Institute at Washington University, said: “This is about as personalised as vaccines can get. The approach we describe is fundamentally different from conventional mutation discovery, which focuses on identifying mutated genes that drive cancer development.
“Instead, we’re looking for a unique set of mutated proteins in a patient’s tumour that would be most likely to be recognised by the immune system as foreign.”
Melanoma tissue samples typically carry 500 or more mutated genes, producing altered proteins. Starting with these mutations, the scientists narrowed their search by identifying proteins not only present in tumours but also likely to be seen as “non-self” by the immune system.
Dr Beatriz Carreno, another member of the Washington University team, said: “You can think of a neoantigen as a flag on each cancer cell.
“Each patient’s melanoma can have hundreds of different flags. As part of validating candidate vaccine neoantigens, we were able to identify the flags on the patients’ cancer cells. Then we created customised vaccines to a select group of flags on each patient’s tumour.”
Seven unique neoantigens were chosen for each tailored treatment and used in conjunction with specialised immune cells called dendritic cells to “wake up” the immune system.
Analysis of blood samples showed that each patient mounted an immune response to the specific neoantigens in their vaccines.
The results suggest a similar approach could be used to produce vaccines against other cancers with high mutation rates, such as those affecting the lung, bladder and bowel.
Dr Linette added: “Our team has developed a new strategy for personalised cancer immunotherapy.
“Many researchers have hypothesised that it would be possible to use neoantigens to broadly activate the human immune system, but we didn’t know that for sure until now. We still have much more work to do, but this is an important first step and opens the door to personalised immune-based cancer treatments.”
The scientists concluded in their paper: “Vaccination against tumour neoantigens appears safe as all three patients are alive and well with no autoimmune adverse events..
“Personalised immunotherapies targeting private somatic tumor alterations may become feasible in the near future.”