mRNA Cancer Vaccines and Therapies: An Overview
The applications of mRNA-based therapies in cancer research represent one of the next groundbreaking steps toward improved cancer treatments. While mRNA usage has played several roles in clinical research, oncology researchers in particular are eager to explore the possibilities of mRNA-based cancer vaccines. Adoptive T Cell therapies, therapeutic antibodies, and immunomodulatory proteins represent just some of the potentially beneficial treatment strategies for successful mRNA cancer trials.
In this blog, we examine how mRNA can impact cancer treatment, the unique challenges associated with working with mRNA, and strategies for researchers proposing mRNA-based cancer trials.
Immunotherapy and Personalized Medicine
Incorporating immunotherapy is becoming increasingly popular in oncology research, creating opportunities for cancer treatments to leverage the body’s own immune system. As researchers continue to identify better cellular targets and expand and improve upon immunotherapy approaches, they become better able to predict patient response and better able to learn from cancer cells’ attack strategies.
Personalized medicine using genetic resequencing techniques, such as cell and gene therapies, enables researchers to create more customized therapies for combatting cancer.
These advancements are part of a larger effort to make cancer research more precise and more effective. Yet there are still significant challenges when implementing such strategies. For example, not all patients respond to immunotherapies; only an estimated 20-40% of patients respond to current immunotherapies.
Additionally, personalized medicine tends to be more difficult to manufacture because of regulatory requirements beyond traditional drug manufacturing requirements. Sites also face difficulty in identifying the right participants for highly specific investigational treatments.
mRNA Cancer Vaccines
mRNA cancer vaccines represent a newer class of vaccines utilizing mRNA’s ability to encode for almost any protein, while maintaining an acceptable safety profile with flexible delivery and production processes.
After injection of such a vaccine, the mRNA instructs cells to produce proteins designed to stimulate an immune response against these same protein targets when they show up in viruses or in tumor cells. The mRNA constructs used in COVID-19 vaccines, for example, direct cells to produce a version of the “spike” protein studding the surface of SARS-CoV-2.
Key challenges to implementing mRNA cancer vaccines includes the need to overcome mRNA’s instability and optimize its delivery. One strategy proposed the use of synthetic mRNA or modified mRNA analogs, which can enhance the stability and protein expression of mRNA.
Adoptive T Cell Therapies
Adoptive T cell therapy is another form of cancer treatment leveraging the patient’s immune system. Some of these approaches involve directly isolating the patient’s immune cells and simply expanding their quantity, while other treatments involve genetically engineering their immune cells to enhance cancer-fighting capabilities.
In addition to challenges in managing related side effects, the promise of cell therapeutics for cancer treatments is also accompanied by challenges in manufacturing and distribution, requiring timely and compliant good manufacturing practice (GMP).
Monoclonal antibodies are lab-engineered immune system proteins. Many monoclonal antibodies are used to treat cancer by targeting specific cell structures regulating cell activity, causing the death of tumor cells.
They’re also functional as a form of immunotherapy, where in some cases, antibodies are coaxed to mark cancer cells so the immune system will better recognize and destroy them. However, current manufacturing and purification processes produce limitations in the production feasibility of therapeutic antibodies, and contributes to increased costs.
Immunomodulators are molecules influencing the pathways regulating the body’s immune system activities. There are currently 16 FDA-approved immunomodulators:
- Nine checkpoint inhibitors
- Four cytokines
- Two adjuvants
- One small molecule with immunomodulatory properties
One of the challenges of using immunomodulatory proteins is their potential impact on cytokine release and liver function. And like other immunotherapies, other significant challenges include inability to predict efficacy as well as high implementation costs.
Strategies for Successful mRNA Trials
Sponsors running mRNA-related clinical trials must submit an investigational new drug (IND) application through the FDA’s Center for Biologics Evaluation and Research (CBER) and receive a biologics IND number prior to initiating human clinical trials.
They must also seek institutional review board (IRB) approval, and often, oversight by an institutional biosafety committee (IBC) is also required. Only after these trials are successful can sponsors seek market approval for mRNA-based products. Comprehensive knowledge of both IRB and IBC requirements is absolutely essential to running a successful mRNA trial.
Having the right clinical trial management toolkit facilitates the operational aspects of your clinical trial, from study startup to closeout. And maintaining quality GxP compliance throughout to safeguard both participant wellbeing and product quality is key to creating successful outcomes.