What are mRNA Vaccines?
mRNA vaccines function by delivering synthetic mRNA into the body’s cells, instructing them to produce specific proteins known as antigens. In the context of cancer, these antigens are typically tumor-associated antigens (TAAs) or tumor-specific antigens (TSAs). The presence of these antigens prompts the immune system to recognize and attack cancer cells expressing them. This approach offers a flexible and rapid method to induce an immune response without exposing the body to live pathogens.
The 3 Types of mRNA Cancer Vaccines
mRNA cancer vaccines can be categorized based on their design and mechanism of action:
- Non-Replicating mRNA Vaccines: These vaccines contain mRNA sequences that encode the desired antigen but do not replicate within host cells. Once delivered, the mRNA is translated into the antigen protein, stimulating an immune response.
- Self-Amplifying mRNA (SAM) Vaccines: SAM vaccines include mRNA that encodes both the antigen and replication machinery, allowing the mRNA to amplify itself within the host cell. This amplification can lead to higher protein expression and potentially a more robust immune response.
- Trans-Amplifying mRNA (taRNA) Vaccines: In this approach, two separate mRNA molecules are delivered: one encoding the antigen and another encoding the replication machinery. The replication machinery amplifies the antigen-encoding mRNA, enhancing antigen production.
These vaccine types can be further tailored to target:
- Tumor-Associated Antigens (TAAs): Antigens overexpressed in tumor cells but also present in normal tissues, which may lead to immune tolerance. Cancer vaccines against TAAs are possibly easier to develop, yet may need immunomodulators as co-treatment to ensure strong immune response.
- Tumor-Specific Antigens (TSAs) or Neoantigens: Antigens arising from tumor-specific mutations, offering high specificity and reducing the risk of targeting normal tissues. They offer stronger immune responses but require personalized medicine approaches for each patient.
- mRNA-Encoded Immunomodulators: mRNA sequences encoding cytokines, antibodies, or immune checkpoint inhibitors to enhance the overall immune response against cancer cells.
What Are The Current Challenges to the Adoption of mRNA Cancer Vaccines?
Despite the potential of mRNA cancer vaccines, several challenges persist:
- Challenge n°1: Antigen Selection
A first challenge in the development of mRNA cancer vaccines is the selection of suitable antigens. The goal is to identify antigens that can trigger a strong and effective immune response, while at the same time avoiding the risk of autoimmunity. This process is highly complex and remains a critical step in vaccine design.
- Challenge n°2: Personalization
Personalization also represents a major obstacle. Creating vaccines that are tailored to the specific characteristics of each tumor requires extensive tumor profiling and rapid manufacturing processes. Both of these steps are time-consuming and costly, making the development of individualized vaccines particularly difficult.
- Challenge n°3: Delivery Systems
Another important challenge is the efficient delivery of mRNA into target cells. The mRNA needs to be protected from degradation and successfully transported into the body, which requires advanced delivery platforms such as lipid nanoparticles. However, since lipid nanoparticles have certain limitations, researchers are also exploring novel systems, including polymer-based methods and extracellular vesicle–mRNA approaches, in order to improve delivery.
- Challenge n°4: Immune Evasion
Tumors have the ability to evade immune detection, which means that combination therapies are often necessary to improve the efficacy of mRNA vaccines. One example is Moderna’s mRNA-4157 (V940), an investigational individualized neoantigen therapy combined with KEYTRUDA® (pembrolizumab), Merck’s anti–PD-1 therapy. This treatment is in Phase III trials for NSCLC and melanoma, and in 2023 it received FDA breakthrough therapy designation for melanoma. Recent clinical data showed a 75% reduction in recurrence for melanoma and lung cancer, suggesting a significant potential in oncology. Another example is BioNTech’s BNT111, developed in collaboration with Regeneron Pharmaceuticals. BNT111 encodes a fixed set of four melanoma-associated antigens intended to trigger a strong and precise immune response. A Phase 2 trial is currently evaluating this vaccine in combination with Libtayo® (cemiplimab), with positive topline results already reported. The program was granted FDA fast track designation and orphan drug status in 2021.
- Challenge n°5: Global Collaborations
Finally, the progress of mRNA cancer vaccines depends on global collaborations. Strengthening partnerships between academic institutions, pharmaceutical companies, and healthcare systems is essential to accelerate clinical development and make these therapies accessible to patients. Some examples of such partnerships include CureVac with the MD Anderson Cancer Center, GSK with the University of Oxford, and the Yale Cancer Center with Merck and Moderna.
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mRNA technology is revolutionizing cancer vaccine development and holds the promise of becoming a pivotal component in the fight against cancer offering a customizable, efficient, and safe approach to stimulating immune responses against tumors. Alcimed will update you continuously on this exciting therapy field. Don’t hesitate to contact our team!
About the author,
Volker, Great Explorer Oncology in Alcimed’s Life Sciences team in Germany
