Is mRNA vaccine, the next immunotherapy frontier?

Utilising mRNA’s versatility to elicit potent immune responses against cancer, these vaccines can prompt the immune system to recognise and eliminate cancer cells displaying these antigens, writes Dr Praveen Kumar Kaudlay

The Covid-19 pandemic brought about unprecedented challenges and sparked remarkable innovations across the globe. Among the most significant breakthroughs was the rapid development of mRNA-based vaccines (messenger ribonucleic acid), which played a crucial role in saving millions of lives and showcased the potential of scientific advancements in addressing global health crises. This success stemmed from years of research into mRNA technology, initially explored for its applications in oncology.

The global cancer burden

Cancer continues to be a pressing global health issue, with incidence rates on the rise. In 2020 alone, approximately 10 million individuals died from cancer worldwide. According to the World Health Organisation (WHO), India reported over 14 million new cases and nearly 9 million cancer-related deaths in 2022. The prevalence of cancer cases has surged, reaching over 32 million within five years. Despite available medical treatments, their impact on reducing the global cancer burden has been minimal, with projections suggesting that the number of cancer cases could rise to 28.4 million by 2040.

Cancer treatment options

Current cancer treatments typically include surgery, chemotherapy, radiotherapy, and immunotherapy. However, these approaches often fall short, particularly because cancer can recur if residual cancer cells remain in the body. mRNA technology holds promise for both early and advanced stages of the disease.

In early stages: In adjuvant settings, mRNA vaccines could target residual tumour cells after standard treatments like surgery and chemotherapy, potentially preventing recurrence through personalised approaches.

In advanced disease: For metastatic cancer, where the disease has spread widely, mRNA may enhance combination therapies, offering new hope for patients in late-stage treatments.

Mechanism of action

Cancer cells possess unique structures on their surfaces, the so-called antigens, which differ from those found on healthy cells and on immune cells. The immune system can identify these antigens, and some may even be specific to an individual’s tumour. Therapeutic cancer vaccines can instruct dendritic cells — crucial components of the immune system — to build specific antigens that prime the immune response to recognise and attack tumour cells displaying these antigens

Personalised cancer vaccines

Research is ongoing to explore various types of cancers where mRNA vaccines could be effectively employed. Further studies are needed to evaluate their efficacy and determine which cancers respond best. Trials are currently underway for cancers such as colorectal, lung, bladder, pancreatic, and kidney cancers. One significant development comes from BioNTech, a German biotech company, which has initiated a Phase 2 trial for a personalised mRNA vaccine candidate targeting melanoma, a form of skin cancer. Early results have indicated a statistically significant improvement in the overall response rate to the vaccine. In the UK, a Memorandum of Understanding was signed between BioNTech and the government, aiming to accelerate clinical trials for personalised mRNA immunotherapies and provide tailored cancer therapies to up to 10,000 patients by 2030. In May 2024, NHS England announced the first patient treated with a personalised vaccine for colorectal cancer as part of a Phase 2 clinical trial. This investigational vaccine, jointly developed by BioNTech and Genentech, analyses individual tumours to identify unique mutations, creating a tailored approach for each patient.

The future of cancer vaccines

Lung cancer is another area where the vaccines have been trialled. Experts are optimistic about the future of mRNA vaccines in cancer treatment. Dr Lennard YW Lee from the University of Oxford highlights the UK’s robust cancer research infrastructure, noting that the foundational work on cancer vaccines has been accelerated post-pandemic, fostering rapid advancements in this field. Dr Elias Sayour, an Associate Professor at the University of Florida, is spearheading research on an experimental mRNA vaccine targeting glioblastoma, a particularly aggressive form of brain cancer that has eluded effective treatment for decades. His team is exploring innovative methods to overcome the tumour’s hostile microenvironment that often obstructs immune responses.

Vaccines have historically transformed medicine, protecting millions from diseases such as measles, mumps, polio, and smallpox.

The global response to Covid-19 demonstrated the power of vaccines in public health. Now, experts believe that mRNA technology could become a vital tool in the fight against cancer, not as a replacement for traditional treatments like surgery, chemotherapy, or radiotherapy, but as an essential addition to the arsenal of immunotherapy options.

The advancements in mRNA vaccine technology offer renewed hope for tackling one of humanity’s most formidable health challenges.

Current treatment innovations
 Checkpoint inhibitors: These drugs enhance the immune system’s ability to combat cancer by blocking proteins that inhibit immune responses.
 CAR-T cell therapy: mRNA can amplify CAR-T cells, which are engineered to target and eliminate cancer cells.
 Next-generation bispecific antibodies: These therapies are designed to target tumours through two different pathways.
 mRNA-based immunotherapies: mRNA-based immunotherapies, often referred to as “cancer vaccines”, are distinct from traditional prophylactic vaccines used against infectious diseases. These cancer vaccines aim to help the immune system recognise and eliminate cancer cells. In early disease stages, they can assist in detecting remaining tumour cells after standard therapies to avert relapse. In advanced stages, they can complement other treatments to reduce the size of large tumours. The successful development of these mRNA-based approaches could revolutionise oncology treatments.

(The author is a consultant haemato-oncologist with a special interest in stem cell transplantation at Royal Wolverhampton NHS Trust, UK. He can be reached at [e-mail].)