The development of mRNA vaccines, best known for the dramatic role they have played in fighting COVID-19, has marked the dawn of a new era in medical innovation. Outside of infectious diseases, mRNA technology is currently leading the pack in the revolutionary treatment of cancer, especially tumor therapy. By the use of the body’s natural immune system to recognize and destroy cancer cells, mRNA vaccines present a personalized, focused, and potentially groundbreaking solution to one of the most feared illnesses among humanity.
This article covers how mRNA vaccines are at the forefront of entering the future of cancer tumor therapy, their mode of action, where the technology is currently at, and the optimism they offer for tomorrow.
The Science Behind mRNA Vaccines for Cancer
mRNA vaccines work by delivering man-made mRNA into cells, instructing them to produce certain proteins that trigger an immune response. In cancer, the proteins are tumor-specific antigens—unique markers on the surface of tumor cells. When the immune system is signaled to these antigens, it mounts a targeted assault, training immune cells, such as T-cells, to target and kill cancer cells without harming healthy tissue.
The Transition from Infectious Diseases to Cancer
The success of mRNA vaccines against COVID-19, led by the likes of Moderna and BioNTech/Pfizer, demonstrated their safety, efficacy, and scalability.
This development spurred investigations into additional applications, with cancer becoming a top target. Initial research in the 1990s investigated mRNA for cancer immunotherapy, but issues related to mRNA instability and inefficient delivery held back progress. Advancements in lipid nanoparticle technology that can encapsulate and shield mRNA for effective delivery into cells have overcome such hurdles, and clinical trials have become possible. Current Advances in mRNA Cancer Vaccines
A number of mRNA-based cancer vaccines have reached the clinic and are demonstrating good results in different types of cancers. BioNTech’s BNT111, for example, combats advanced melanoma by expressing tumor-specific antigens to elicit an immune response. Early-stage trials have shown promising results with some patients showing tumor regression upon combining the vaccine with checkpoint inhibitors—drugs that allow the immune system to target cancer cells more effectively.
Moderna’s mRNA-4157 (also V940) is another contender, as a tailored neoantigen vaccine for melanoma and other solid cancers. In a phase 2 trial, paired with Merck’s Keytruda, mRNA-4157 decreased the risk of recurrence or death by 44% among high-risk melanoma patients when compared to the use of Keytruda alone. That success has fueled additional trials among cancers such as non-small cell lung cancer and pancreatic cancer.
In addition to individualized vaccines, “off-the-shelf” mRNA vaccines are currently being created to address broad tumor antigens that are common among patients, for example, in some breast or lung cancers. These vaccines are intended to increase accessibility and lower costs, and thus make mRNA treatment available to a greater population.
Benefits of mRNA Vaccines in Cancer Treatment
The hope of mRNA vaccines in cancer therapy is that they have certain benefits.
First, their individualized nature makes them compatible with precision medicine, aimed at the unique mutations of a patient’s cancer. This is especially well-suited to high-mutational burden cancers like melanoma or lung cancer. Second, mRNA vaccines are very fast to manufacture, frequently within several weeks of tumor sequencing, allowing for intervention in a timely manner. Third, their capacity for inducing both innate and adaptive immunity provides a valuable flexibility in the battle against cancer’s complexity. Furthermore, mRNA vaccines are well-tolerated, with side effects such as mild fever or soreness at the injection site less severe than those associated with conventional chemotherapy or radiation. Their non-integrating character—mRNA does not modify the DNA of the patient—only adds to their safety profile.
Challenges and Future Directions
Although promising, mRNA cancer vaccines have substantial challenges. Tumor heterogeneity, even in a single patient, is a challenge since the targeted antigens may not be expressed in all cancer cells. Also, the tumor microenvironment tends to impair immune responses such that the vaccines might require combination therapies with agents such as checkpoint inhibitors or other immunomodulators to achieve effectiveness.
Cost and scalability are issues, especially for personalized vaccines, where tumor sequencing and customized manufacturing are needed. Off-the-shelf vaccines can possibly cut this, but equitable access worldwide will necessitate creative solutions in production and distribution.
Scientists are experimenting in the future on how mRNA vaccines can be advanced. They are combining them with other immunotherapies, such as CAR-T cell therapy, to make them stronger. Artificial intelligence is also becoming more efficient in the identification of neoantigens, which is also making the design of vaccines more accurate, and mRNA vaccines are also being researched in adjuvant use during cancer surgery, preventing the recurrence by killing any still present cancer cells.
