Personalised vaccines trialled for skin cancer treatment

Researchers from Edith Cowan University (ECU) are leading groundbreaking global trials which could change how we treat cancer in the near future, the results of which were recently presented by Professor Adnan Khattak at the 2023 American Society of Oncology (ASCO) congress in Chicago.

Khattak’s presentation outlined how survival and disease recurrence rates among people who’d had high-risk skin cancers (melanomas) removed improved significantly when an mRNA vaccine tailored to suit an individual’s tumour genetics was added to common immunotherapy treatment. He said the trial began as a way of trying to address the shortcomings of current treatments.

“The current standard of care is immunotherapy using an antibody known as pembrolizumab,” he said.

“There are two main issues: first, despite having active immunotherapy for stage three melanoma, about half of patients will relapse at five years. And secondly, it’s a very crude approach: currently if I treat 10 new high-risk melanoma patients, I give them the same drug. It’s not rocket science that it’s going to work for some but not others, and some may see side effects and others may not.”

Though vaccines are typically associated with disease prevention, in this instance an mRNA vaccine was used to treat people who have already been diagnosed with melanoma. Samples of tissue are taken and analysed to identify neoantigens — proteins which form on cancer cells, and which are unique to an individual’s tumour. Up to 34 neoantigens may be identified, which are then added to an mRNA molecule and added to a vaccine. The result is a personalised cancer treatment, with the neoantigens most likely to develop an immune response to help the patient’s body fight cancer.

After 18 months, cancer-free survival among patients who received the vaccine and the immunotherapy treatment was 78.6%, compared to 62.2% of those who only received the immunotherapy. Two years after treatment, only 22.4% of patients who had received the vaccine/immunotherapy combination had either died or seen a recurrence of the disease, which rose to 40% for the immunotherapy-only group. Overall, after an average of two years those who received the vaccine saw a 44% lower risk of death or melanoma returning to the same area of the body, and a 65% reduction in the risk of death or the cancer returning in a different area of the body.

Khattak said the vaccine appeared to be more effective after an extended period of time and multiple doses, noting, “The survival rate between the two groups is the same after 40 weeks, so early relapses happen for both.

“But after the first 40 weeks, by then the patients have had two or three vaccine doses and the anti-tumour effect really kicks in.

“We see quite a significant proportion of patients relapsing after they finish pembrolizumab, whereas we’re not seeing such late relapses in patients who have done the double treatment.”

Khattak will soon lead a new global trial of the treatment that will include even more participants, some with earlier stages of melanoma. If successful, the trial could be the starting point of a new approach to cancer treatment, beyond just melanoma.

“This is going to be the stepping stone for a number of trials, because now they have expanded it into lung cancer, kidney cancers and also into gastrointestinal cancers,” Khattak said.

“This has the potential of becoming a new standard of care moving forward.”

Image credit: iStock.com/Artur Plawgo