A personalized cancer vaccine prototype has shown great promise in a phase 1 trial against different types of cancer, including some that have a high risk of reappearing. I’m not sure if everybody here is old enough to remember this, but there used to be a time when “finding the cure to cancer” was seen as the be-all-end-all of human ingenuity. Back when my family was still toying with the idea of sending me off to medical school, my grandparents would cheer me on saying that maybe I’ll be the one to discover it — with everybody sharing the silent knowledge that such a wonder would not be possible in our lifetime. So it’s a very surreal experience to see just how far along we’ve come towards that goal. A new paper reports that personalized vaccines against cancers — compounds created from the genetic data of individual patients and their tumors — are effective against the disease, safe to use, and show promise against commonly recurring cases. Individually tailored “While immunotherapy has revolutionized the treatment of cancer, the vast majority of patients do not experience a significant clinical response with such treatments,” said study author Thomas Marron, MD, Ph.D., Assistant Director for Early Phase and Immunotherapy Trials at The Tisch Cancer Institute and Assistant Professor of Medicine at the Icahn School of Medicine at Mount Sinai. “Cancer vaccines, which typically combine tumor-specific targets that the immune system, can learn to recognize and attack to prevent recurrence of cancer. The vaccine also contains an adjuvant that primes the immune system to maximize the efficacy.” This class of vaccines was developed with help from the Mount Sinai computational platform OpenVax, created by a group which “develops open-source software for designing personalized cancer vaccines”. In order to create these personalized vaccines, Dr Marron and his team sequenced tumor and germline DNA, alongside tumor RNA, from each patient. They also used this data to help predict whether each individual’s immune system would recognize the vaccine’s targets or not. For the trial, the participants received 10 doses of the personalized vaccine over a six-month period after undergoing any standard cancer treatment (for example surgery). It was administered alongside an immunostimulant (or an ‘adjuvant’). This adjuvant, poly-ICLC, is a synthetic, stabilized, double-stranded RNA capable of activating multiple innate immune receptors, making it the optimal adjuvant for inducing immune responses against tumor neoantigens,” said study author Nina Bhardwaj. Thirteen participants received the prototype vaccine. Out of them, 10 had been diagnosed with solid tumors, and 3 had multiple myeloma. All of them had, statistically speaking, a high chance of seeing a resurgence of the disease following treatment. However, after a mean follow-up interval of 880 days, four of the participants were still cancer-free, four were receiving subsequent lines of therapy, four had died, and one chose to not continue the trial. The vaccine was tolerated well upon administration, with only one-third of the participants developing minor reactions “Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” said Dr. Bhardwaj. “We have therefore developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, […] when patients have minimal — typically microscopic — residual disease. Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types.” The most exciting area of the finding relates to types of cancer that have a high risk of recurrence, such as lung and bladder cancers. Personalized vaccines could finally give us a safe and efficient means of fighting them, and preventing them from reforming. Still, these results were from a phase 1 trial, whose main aim is to determine whether a drug candidate is safe to use. While the potential benefits of the compound were noticed, determining how best to administer it for the greatest effect is the object of the phase 2 trial — meaning, we’ll have a good idea of what this vaccine can and can’t do quite soon. The findings have been presented during Week 1 of the virtual AACR Annual Meeting 2021, held April 10-15. Source
