mRNA—From COVID-19 Treatment to Cancer Immunotherapy

Abstract

This review provides an overview covering mRNA from its use in the COVID-19 pandemic to cancer immunotherapy, starting from the selection of appropriate antigens, tumor-associated and tumor-specific antigens, neoantigens, the basics of optimizing the mRNA molecule in terms of stability, efficacy, and tolerability, choosing the best formulation and the optimal route of administration, to summarizing current clinical trials of mRNA vaccines in tumor therapy.

Intradermal Delivery of Naked mRNA Vaccines via Iontophoresis

“…The United States Food and Drug Administration (FDA) approved two mRNA vaccines (mRNA-1273 and BNT 162b2) that have shown great potential to combat COVID-19 [ 1 , 2 ]. After the success in controlling COVID-19, the development of mRNA-based personalized cancer vaccines started to attract considerable attention [ 3 , 4 ]. More than twenty mRNA-based anticancer immunotherapies are currently being investigated in clinical trials [ 5 ].…”

The Role of Human Endogenous Retroviruses in Cancer Immunotherapy of the Post-COVID-19 World

“…A well-known blockbuster, linked with the Nobel Prize in Medicine in 2018, is the FDA-approved immune checkpoint inhibitors (ICIs), which release the brakes that prevent T lymphocytes from killing cancer cells. Intriguingly, the pandemic propelled mRNA vaccines, a distinct class of immunotherapeutics, into the limelight as a cost-effective means to harness our immune systems against this global viral threat [1]. Encouraged on the one hand by the favorable data on the safety and efficacy of mRNA vaccines for SARS-CoV-2, and on the other hand by the success story of ICIs, researchers are now using the 'pandemic heritage' as a springboard to design personalized, mRNA vaccine-based treatments for several cancer types [1].…”

“…Intriguingly, the pandemic propelled mRNA vaccines, a distinct class of immunotherapeutics, into the limelight as a cost-effective means to harness our immune systems against this global viral threat [1]. Encouraged on the one hand by the favorable data on the safety and efficacy of mRNA vaccines for SARS-CoV-2, and on the other hand by the success story of ICIs, researchers are now using the 'pandemic heritage' as a springboard to design personalized, mRNA vaccine-based treatments for several cancer types [1]. Advantageously, mRNA molecules induce both humoral and cellular immune responses, and are well-tolerated and easily degradable, while their production is fast, scalable, and inexpensive.…”

“…The results from early clinical trials with mRNA vaccines as monotherapy and in combination with ICIs are auspicious [2]. A growing number of recent studies highlight the evolution and progress of cancer mRNA vaccines in the clinical setting [1,3,4], as well as the development of delivery systems, like lipid or polymeric nanoparticles, and protamines [5]. A crucial aspect for the design of mRNA vaccines is the identification of targets, which ideally need to be immunogenic and exhibit tumor-restricted expression [5].…”