mRNA-based cancer therapies hold immense potential to revolutionize cancer treatment. However, there are several challenges that need to be addressed for the clinical use of mRNA in cancer therapy. mRNA itself is inherently unstable and can be immunogenic. The recent advances in nanotechnology, particularly the development of lipid nanoparticles (LNPs), have made mRNA-based cancer therapies feasible.
In general, mRNA-based cancer therapies share a common principle: mRNA is translated into proteins that can inhibit tumor growth or induce or enhance anti-tumor immune responses.
- Direct Encoding of Anti-Cancer Proteins: mRNA can be designed to directly encode anti-cancer proteins. For example, it can encode proteins that have anti-tumor effects.
- Encoding Tumor Neoantigens and Cytokines: mRNA can be used to encode tumor neoantigens or cytokines within cancer cells or the tumor microenvironment. These neoantigens and cytokines can activate immune responses against cancer.
- Gene Expression Regulation: mRNA technology can be used to interfere with the expression of critical genes that promote cancer cell survival.
- Enhancing CAR-T and TCR-T Therapies: mRNA technology can be used to enhance Chimeric Antigen Receptor T-cell (CAR-T) and T-cell Receptor T-cell (TCR-T) therapies.
Researchers are also exploring new types of mRNA, such as self-amplifying mRNA (saRNA), trans-amplifying RNA (taRNA), and circular RNA (circRNA), along with methods for long-term storage of mRNA nanoparticles, delivery routes, and organ-selective translation. These explorations aim to make mRNA-based cancer therapies even more effective and applicable to a wide range of cancer types for the benefit of patients.
Types of mRNA and Delivery Platforms
- Classic mRNA: These are structurally similar to endogenous mRNA and are easy to synthesize. They can be optimized for stability, transcription efficiency, and immune response.
- New mRNA Types: New mRNA types like saRNA and taRNA have more stable structures and higher protein expression efficiency. They are being explored for their advantages in cancer therapy.
Non-Viral mRNA Delivery: While viral vectors have been traditionally used to deliver mRNA, non-viral delivery systems like lipid nanoparticles (LNPs) and cationic polymers are being researched to overcome the limitations of viral vectors.
Encoding Tumor Antigens and Neoantigens: mRNA-based cancer vaccines can be designed to encode tumor-related antigens (TAAs) and tumor-specific antigens (TSAs) to activate immune responses against cancer cells.
Encoding Cytokines: mRNA can encode cytokines that play a significant role in regulating the tumor microenvironment and immune responses. This can enhance the effectiveness of cancer immunotherapy.
Using mRNA for Gene Editing with Cas9: mRNA encoding CRISPR-Cas9 components can be used for gene editing in cancer cells, potentially offering a safer and more controlled approach.
Encoding CAR or TCR: mRNA can be used to modify T cells with chimeric antigen receptors (CAR) or T-cell receptors (TCR) for immunotherapy. This approach can reduce the risk of genomic alterations associated with traditional viral transduction.
In summary, mRNA-based cancer therapies have shown great promise in preclinical and early clinical studies. These therapies offer the potential for precise, personalized treatment approaches for various cancer types. Ongoing research and development are expected to further optimize mRNA-based cancer therapies and expand their application in cancer treatment.