The rapid development of highly efficacious vaccines utilizing messenger RNA (mRNA) platforms has proven highly successful in the last year. Prior to the pandemic, mRNA vaccines were primarily being developed to target a variety of cancers. The development of mRNA vaccines for oncology indications proves significantly complex relative to infectious diseases. Where infectious diseases are concerned, target sites such as S-proteins are easier to target owing to the fact they are foreign bodies. With cancerous tissue, the heterogeneity between cancer cells makes suitable target selection difficult. For this reason, cancerous tissue is extracted from the patient and sent for sequencing to identify the unique cancer-producing mutations. The vaccine design is informed by the most frequently occurring mutations, and the codes for these mutations are then loaded onto a mRNA molecule. The vaccine is then expected to instruct the patient’s own cells to produce protein fragments containing the mutations, such that the patient’s immune system recognizes the aberrant cancer cells to elicit an immune response against them.
As shown in Figure 1, early mRNA oncology vaccine trials proved to be unsuccessful, with a significant proportion of studies (55.5%) being withdrawn or terminated from 2009 to 2016. Enrollment issues and poor efficacy proved to be the greatest barriers during this period. From 2017 onwards, the proportion of terminations and withdrawals fell drastically to 10.3%, potentially highlighting improvements in mRNA vaccine development in oncology. The greatest year-on-year decline in the total number of studies was observed between 2019 and 2020, a period where many sponsors redirected their resources to vaccine development for COVID-19.
Following the success of Moderna’s and Pfizer-BioNTech’s vaccines against COVID-19, the number of mRNA-based vaccine therapeutics in clinical trials for oncology has increased significantly, with 2021 already scheduled to have the greatest number of clinical trials, although a significant proportion of these studies (54.4%) were testing COVID-19 vaccines in cancer patients. Allowing for the removal of COVID-19 trials in cancer patients, as shown in Figure 1, 2021 marks the year with the second-highest number of oncology mRNA vaccines trials, with more studies yet to be announced.
BioNTech is the top sponsor for mRNA vaccines in oncology, with involvement in 18% of trials with a range of vaccines (BNT-112, BNT-113, BNT-114, BNT-115) targeting various indications. CureVac holds second place and is the sponsor that initiated the earliest clinical studies investigating mRNA vaccines in oncology. Nonetheless, CureVac only has one clinical trial in ongoing status. Previous studies were either terminated or withdrawn, with only two trials reaching completion. Notably, CureVac has also recently published a disappointing readout for its pivotal Phase II/III study for its mRNA COVID-19 vaccine CVnCoV, displaying only a 47% efficacy against COVID-19, around half the value of Moderna’s and Pfizer’s mRNA COVID-19 vaccines. While it’s evident that the COVID-19 pandemic has rapidly accelerated the development of mRNA vaccines for infectious disease, applications in oncology are in their infancy, with the furthest developed vaccine only in Phase II status. As progress and knowledge continue to advance, mRNA vaccines may have the scope to be a valuable tool in the fight against cancer.