Potential of mRNA vaccines to become versatile cancer vaccines

Abstract

For centuries, therapeutic cancer vaccines have been developed and tried clinically. Way back in the late 19^th century, the Father of Immunotherapy, William Coley had discovered that bacterial toxins were effective for inoperable sarcomas. In the 1970s, the Bacillus Calmette-Guérin (BCG) vaccine was repurposed, e.g., for advanced melanomas. Then, therapeutic cancer vaccines based on tumor-associated antigens (found on the surfaces of cancer cells) were tried clinically but apparently have not made a really significant clinical impact. For repurposed pathogen vaccines, only the BCG vaccine was approved in 1989 for local application to treat nonmuscle-invading bladder cancers. Although the mildly toxic vaccine adjuvants deliberately added to conventional pathogen vaccines are appropriate for seasonal applications, when repurposed for continual oncology usage, toxicity may be problematic. In 2010, even with the approval of sipuleucel-T as the very first cancer vaccine (dendritic cell) developed for designated prostate cancers, it has also not made a really significant clinical impact. Perhaps more "user friendly" cancer vaccines should be explored. As from approximately 30 years ago, the safety and effectiveness of mRNA vaccination for oncology had already been studied, the current coronavirus disease 2019 pandemic, though disastrous, has given such progressively advancing technology a kickstart. For oncology, other virtues of mRNA vaccines seem advantageous, e.g., rapid and versatile development, convenient modular design, and entirely cell-free synthesis, are being progressively recognized. Moreover, mRNAs encoding various oncology antigens for vaccination may also be tested with the combi-nation of relatively non-toxic modalities of oncology treatments, e.g., metformin or metronomic (low-dose, prolonged administration) chemotherapy. Admittedly, robust clinical data obtained through good quality clinical trials are mandatory.

Keywords: Cancer vaccine; Cyclophosphamide; Metformin; Metronomic chemotherapy; mRNA vaccine; Myocarditis; Tumor microenvironment

Core Tip: Although vaccines are effective for pathogen prevention and cancers, hitherto, oncology vaccines have not yet made a very significant clinical impact. Currently, as mRNA vaccines already have a proven safety profile, it is highly appropriate to further develop the decades-old mRNA technology for oncology. Compared to other approved cancer vaccines, oncology mRNA vaccines may be more versatile, pragmatic, affordable, and effective. To combat the notoriously resistant tumor microenvironment, the probable mutual enhancement effects with, e.g., metronomic chemotherapy should be fully explored, especially as no significant added toxicity is anticipated. Clearly, undertaking much more research work (especially clinical) is mandatory.