Current advance and future of mRNA vaccine in cancer therapy

1 .Introduction

Cancer--immunotherapy

-Immunotherapy is a cancer treatment that uses your body's immune system to find and destroy cancer cells. Your immune system identifies and destroys intruders, including cancerous cells. Immunotherapy boosts your immune system so it can do more to find and kill cancer cells.

Vaccine-mRNA vaccine

-The mRNA vaccines don't contain the virus that causes disease. Instead, they contain “messenger molecules” (mRNA) that give your body instructions that are kind of like a special recipe. The instructions tell your cells how to make a piece of the protein from a virus, such as the virus that causes COVID-19.

2.structure of mRNA vaccine :

The basic structure of mRNA, same as eukaryotic mRNA, is made up of (i) protein encoding ORF, surrounded by (ii) 5′ and 3′ UTRs, and (iii) a 7-methyl guanosine 5′ cap structure and (iv) a 3′poly(A) tail at the end sides (Verbeke et al. 2019; Schlake et al. 2012; Sahin et al. 2014) (Fig. 1). These components can be modified or altered to increase the stability, translation efficiency, and immune-stimulatory feature of mRNA . The translation and stability of mRNA can be improved and critical tasks have been undertaken to identify desirable mRNA elements.

mRNA vaccines represent a groundbreaking technology in the field of vaccine development, offering a versatile platform. for preventing and treating infectious diseases, as well as certain types of cancer. These vaccines leverage the body's natural processes to produce antigens and elicit an immune response. Here, we delve into the classification of mRNA vaccines based on the types of mRNA they use and the routes of administration.

Classification Based on Types of mRNA

Non-Replicating mRNA (nRNA) Vaccines

Non-replicating mRNA (nRNA) vaccines are the most common type of mRNA vaccine used today. They contain a single-stranded RNA molecule that encodes the antigen of interest, typically a viral protein. Upon injection, the nRNA enters the cytoplasm of host cells, where it is translated into the antigen. This antigen is then presented on the cell surface, triggering an immune response.

● Advantages:

○ Rapid production and scalability.

○ Minimal risk of integrating into the host genome.

○ Can be designed quickly in response to new pathogens.

● Challenges:

○ Short half-life in the body.

○ Requires stabilization and delivery technologies, such as lipid nanoparticles (LNPs), to protect the mRNA and facilitate cellular uptake.

Self-Amplifying mRNA (SAM) Vaccines

Self-amplifying mRNA (SAM) vaccines contain an RNA molecule that not only encodes the antigen but also includes a replication mechanism. This means that once inside the cell, the SAM RNA can replicate itself, producing multiple copies of both the antigen and the replication machinery.

● Advantages:

○ Higher antigen expression levels due to amplification.

○ Potentially lower doses required.

○ Longer duration of antigen expression.

● Challenges:

○ More complex manufacturing process.

○ Greater risk of adverse effects due to higher antigen levels.

Trans-Amplifying mRNA Vaccines

Trans-amplifying mRNA vaccines are a newer concept in mRNA vaccine technology. These vaccines consist of two components: a non-replicating mRNA that encodes the antigen and a separate self-amplifying mRNA that drives the expression of the antigen. The self-amplifying component provides the replication machinery, while the non-replicating mRNA encodes the antigen.

● Advantages:

○ Allows for high antigen expression levels without the need for high doses.

○ Potential for greater safety and control over antigen expression.

● Challenges:

○ Complex design and production.

○ Limited clinical experience compared to other mRNA vaccine types.

Classification Based on Route of Administration

The route of administration for mRNA vaccines can influence the efficacy, safety, and distribution of the vaccine within the body. Here are the various routes of administration:

Subcutaneous Injection

Subcutaneous injections deliver the vaccine into the layer of skin just below the dermis. This route is suitable for vaccines that do not require deep tissue penetration and can stimulate a robust immune response at the site of injection.

● Advantages:

○ Easy to administer.

○ Can stimulate local immune responses.

● Challenges:

○ May not be effective for systemic diseases.

Intradermal Injection

Intradermal injections are administered directly into the dermis layer of the skin. This route is advantageous for vaccines that aim to activate skin-resident immune cells, such as dendritic cells, which are important for initiating immune responses.

● Advantages:

○ Direct delivery to immune cells.

○ Can enhance immune response.

● Challenges:

○ Requires precise injection technique.

○ May cause more local inflammation.

Intramuscular Injection

Intramuscular injections are the most common route for mRNA vaccines, including the COVID-19 vaccines. This route ensures rapid absorption and distribution of the vaccine throughout the body, leading to efficient antigen expression and immune activation.

● Advantages:

○ Rapid systemic distribution.

○ Well-established injection technique.

● Challenges:

○ May cause muscle soreness.

Intravenous Injection

Intravenous injections deliver the vaccine directly into the bloodstream. This route is less common for mRNA vaccines but can be useful in specific therapeutic contexts, such as cancer treatment.

● Advantages:

○ Immediate systemic distribution.

○ Suitable for systemic diseases.

● Challenges:

○ Requires medical supervision.

○ Higher risk of adverse effects.

Intranodal Injection

Intranodal injections target the lymph nodes directly, which are key sites for immune cell activation. This route can potentially enhance the immune response by delivering the antigen to the very place where immune cells are activated.

● Advantages:

○ Direct delivery to immune cells.

○ Enhanced immune response.

● Challenges:

○ Requires precise targeting.

○ Limited clinical experience.

6. Intratumoral Injection

Intratumoral injections deliver the vaccine directly into a tumor. This approach is primarily used in cancer immunotherapy, where the goal is to stimulate an immune response against the tumor cells.

● Advantages:

○ Localized immune response.

○ Can enhance antitumor immunity.

● Challenges:

○ Requires tumor access.

○ May not be feasible for all tumor types.

7. Intrathecal Injection

Intrathecal injections deliver the vaccine into the cerebrospinal fluid, which surrounds the brain and spinal cord. This route is primarily used for conditions affecting the central nervous system.

● Advantages:

○ Direct delivery to the central nervous system.

○ Suitable for CNS diseases.

● Challenges:

○ Requires specialized administration

○ Higher risk of adverse effects