VACCINE therapies for cancers have been a focus for developments in personalised medicine, and a recent Phase I trial has shown promising results for both safety and benefit.
The study, conducted at the Icahn School of Medicine at Mount Sinai, New York, New York, USA, developed a personalised cancer vaccine by first sequencing the tumour and germline DNA and tumour RNA for each patient. The team then utilised a Mount Sinai computational platform, OpenVax, which helps to identify and prioritise immunogenic targets for the vaccine.
The study author, Thomas Marron, The Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, explained that cancer vaccines “typically combine tumour-specific targets that the immune system can learn to recognise and attack to prevent recurrence of cancer. The vaccine also contains an adjuvant that primes the immune system to maximise the efficacy.” This adjuvant immunostimulant, elaborated co-author Nina Bhardwaj, The Tisch Cancer Institute at Mount Sinai, was “a synthetic, stabilised, double-stranded RNA capable of activating multiple innate immune receptors, making it the optimal adjuvant for inducing immune responses against tumour neoantigens.”
In this Phase I clinical trial, patients received standard care for their cancer type, followed by 10 doses of a personalised cancer vaccine over a 6-month period. Rather than target populations with metastatic disease, the trial built from findings in immunotherapy that saw success in patients with less cancer spread, so provided vaccine therapy immediately following standard-of-care therapies when minimal residual disease states were expected.
Prior to the vaccine, the studied patients had statistically likely high rates of recurrence: 10 patients had solid tumour diagnoses and three patients had multiple myeloma. After a mean follow-up period of 880 days, four patients had no evidence of return of cancer, four patients were receiving further anticancer therapies, four had died, and one patient elected not to continue the trial.
The primary goal of the clinical trial was safety and tolerability, which were satisfactorily met; approximately one-third of patients experienced minor injection-site reactions. The lower-than-expected recurrence rates were promising for the efficacy of the personalised cancer vaccines, along with blood results suggesting immune responses from the vaccine or improved responses to subsequent immunotherapy in some of the studied patients; however, further studies are needed.