mRNA for cancer therapy and prevention: 4 promising developments in clinical trials to keep an eye on

Published on 21 February 2024 Read 25 min

Messenger RNA (mRNA) is a type of RNA molecule that is produced from DNA through a process called transcription, carries genetic information, and plays a crucial role in the process of protein synthesis. The possibility to produce synthetic mRNA encoding specific antigens makes it a very interesting and versatile tool for the treatment and/or prevention of various diseases like, cancer or infections. mRNA vaccines typically use small pieces of mRNA to stimulate an immune response against a specific target, like a virus or pathogen. The mRNA in the vaccine encodes a protein or piece of protein, that once it enters cells instructs the cells to produce copies of the protein and display it on the surface, which consequently triggers an immune response against it. The vaccine is encased in a protective lipid nanoparticle to help it enter cells and avoid being degraded by the body’s immune system. Once it has done its job, it is designed to be quickly degraded so there is no long-term effect on the body’s cells. Based on this, messenger RNA offers two different approaches to be used in cancer therapy. In this article, Alcimed explores the different approaches and the latest promising advances in cancer treatment with mRNA.

Main approaches to the use of mRNA in cancer therapy

mRNA as a preventive vaccine against cancer

Two main approaches can be described.  The first is to use mRNA vaccines as preventive vaccines to stimulate an immune response against cancer cells, which often have unique proteins or mutations that can be targeted by the immune system, but are also able to develop mechanisms to evade immune detection. mRNA vaccines can be designed to stimulate the immune system to recognize and attack cancer cells.

mRNA as a cancer treatment

The second approach is about therapeutic cancer vaccines to use mRNA to deliver therapeutic modalities directly to cancer cells, or to interfere with specific gene or signalling pathways that are important for cancer growth and survival. Because Messenger RNA can be rapidly produced and easily modified, it offers a potentially flexible and adaptable platform for cancer therapy.

Read also : mRNA vaccine development in oncology: what will the future bring?

4 promising developments in clinical trials of mRNA for cancer therapy

Cancer vaccine aimed to prevent triple-negative breast cancer

The Cleveland Clinic has announced the next step in their ongoing clinical trial for a preventive breast cancer vaccine. The trial will now move on to phase 1b, which will involve more participants and evaluate the vaccine’s effectiveness, safety and immune response, in preventing triple-negative breast cancer in women who are at high risk for developing the disease. The vaccine targets a protein called α-lactalbumin, which is usually present in breast tissue exclusively during pregnancy but no longer after lactation in healthy and aging breast tissue, in contrast most triple-negative breast cancer presents with α-lactalbumin expression in the tissue. The vaccine is designed to induce an immune response to attack forming tumors and prevent them from growing further.

Personalized mRNA immunotherapies to treat cancer

BioNTech, who developed the first authorized COVID-19 vaccine with Pfizer, has announced a multi-year strategic collaboration with the UK government focusing on three strategic pillars: cancer immunotherapies, infectious disease vaccines, and expansion of BioNTech’s UK footprint. Part of this Memorandum of Understanding is the goal to accelerate clinical trials for personalized mRNA immunotherapies to provide personalized cancer therapies for up to 10.000 patients by end of 2030.

Learn more about how our team can support you in your projects related to messenger RNA >

Innovative therapy for the treatment of high-risk melanoma patients after complete resection

The FDA has granted breakthrough therapy designation to the combinatory treatment with Merck’s KEYTRUDA® and Moderna’s mRNA-4157/V940 based on encouraging results from phase 2b trials. This classification is given to accelerate the development and evaluation of medications that aim to treat a severe illness, and if preliminary clinical evidence suggests that the drug might show significant progress over existing therapies in at least one important clinical endpoint. mRNA-4157/V940 is an innovative experimental cancer vaccine that utilizes a solitary synthetic mRNA to encode up to 34 neoantigens, specifically tailored and synthesized to the patient’s tumors distinct mutational pattern. After administering the vaccine, the mRNA-encoded neoantigen sequences undergo natural cellular antigen processing and presentation, which is a crucial stage in adaptive immunity. The combination of KEYTRUDA®, Merck’s anti-PD1 therapy, and mRNA-4157/V940 showed a significant and meaningful improvement in the primary endpoint of recurrence-free survival (RFS) compared to KEYTRUDA® alone when administered to patients with stage III & IV melanoma following complete resection.

Positive results from BNT113 trials involving combination therapy with pembrolizumab

BNT113 is an mRNA vaccine used in cancer therapy that encodes proteins E6 and E7 typically found in HPV16-positive solid tumors. Its purpose is to activate a potent and precise immune response in patients diagnosed with HPV-16 positive head and neck squamous cell carcinomas (HNSCCs). In a non-commercial phase I/II study, HARE-40, the administration of BNT113 demonstrated the elicitation of strong T-cell responses targeted against specific antigens in patients. The following phase II study, AHEAD-MERIT, is currently investigating the efficacy of BNT113 combined with Merck’s pembrolizumab, a PD-1 inhibitor, versus monotherapy with pembrolizumab in patients suffering from unresectable recurring metastatic HPV-positive, PD-1 positive HNSCCs and is showing first promising results.

mRNA cancer vaccines bring many advantages, such as the ability to elicit a robust protective immune response, flexibility, no oncogenic potential, rapid and large-scale production, relatively low production costs, well tolerated, and versatility making them a powerful and versatile form of immunotherapy. The course and possible success of current trials holds high hopes for new treatment options to be available in the near future. Alcimed is closely following the future developments in the field of and novel cancer treatments and is ready to support you on these topics. Don’t hesitate to contact our team!

About the author,

Volker, Great Explorer Oncology in Alcimed’s Healthcare team in Germany

Lisa, Consultant in Alcimed’s Healthcare team in Germany

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