Lung cancer is one of the most frequently diagnosed malignancies and the leading cause of cancer death worldwide. Its diagnosis is usually made in an extensive or metastatic stage, with the main risk factor for the disease being smoking. About 85% of cases are categorized as non-small cell lung cancer. Recent years have seen significant leaps in both the diagnosis and treatment of lung cancer with notable advances in screening, the use of new minimally invasive diagnostic techniques, and the release of more effective and specific treatments for the disease. NSCLC patients eligible for targeted therapies or immunotherapy are now surviving longer with 5-year survival rates ranging from 15% to 62.5%, depending on the subtype of lung cancer, while also having a better quality of life.

The period of the pandemic was an important springboard for the further development and better understanding of the action of a particular category of personalized therapy of this vaccines and more specifically mRNA vaccines, which was already known in the community of Pathological Oncologists. As early as the 1990s it was known that injecting mRNA into cells in the laboratory had the potential to modify and enhance the immune system. The first successful clinical trial of a vaccine in solid tumors began in 2008 and involved patients with metastatic prostate cancer. To create the vaccine, cells from the patient’s own immune system were collected and after special modification were re-injected into the patient’s body, enhancing the body’s immune response against the tumor. So in 2013, the first approval of a vaccine as an anti-cancer treatment takes place.

In the following years, significant leaps in the development and study of mRNA vaccines mainly by evaluating their safety and potential efficacy in phase I and recently phase II clinical trials in both non-small cell lung cancer and other common neoplasms. In recent months there has been extensive discussion regarding the new “effective” therapeutic weapon in non-small cell lung cancer, discussion concerning an early phase multicenter study to evaluate the activity of an mRNA vaccine. We should make it clear that it concerns a clinical trial evaluating a new anticancer treatment, potentially effective or not in the future, which in no way can replace already approved effective options for non-small cell lung cancer as it is in the early stages of study.

What we know about mRNA vaccines and more specifically about the new mRNA vaccine and clinical trials being studied in non-small cell lung cancer

• More than 20 mRNA vaccines are being studied in early phase clinical trials and in the laboratory in various solid tumors such as colon and breast cancer, but we do not know their effectiveness and safety in the treatment of cancer
• The aim of administering mRNA vaccines is mainly to strengthen our immune system so that it can successfully fight tumor cells
• mRNA vaccines are enthusiastically received by the scientific community mainly because they have advantages in terms of good patient tolerance to their administration with usually treatable and transient side effects. Also, they do not ‘get’ into the patient’s DNA so they have little risk of creating new mutations, they are easily eliminated from the body and they have fast and relatively cheap production. Above all, they strengthen all types of immunity, with the result that its activation also lasts
• Regarding new mRNA vaccines in non-small cell lung cancer the best known is a vaccine containing 6 liposomally modified mRNAs, each of which codes for a different tumor antigen often expressed in non-small cell lung carcinoma targeting the strengthening the immune response aimed at destroying cancer cells
• Early results, mainly in the laboratory, report a positive safety profile which led to the design of a phase I and then a phase II clinical study to evaluate the efficacy and safety of the vaccine
• The current clinical trial is enrolling patients with both early and advanced non-small cell lung cancer and receiving it alone, in combination with immunotherapy, or in combination with immunotherapy and chemotherapy
• Administration of the specific mRNA vaccine is carried out intravenously in 6 initial weekly doses and then every 3 weeks for a total period of up to 54 months
• The first administration of the vaccine in the study took place in Summer 2024 in the UK and the current study is being conducted in 34 Oncology Centers in the UK, USA, Germany, Spain and Turkey
• In our country, research centers are conducting a similar multicenter phase II clinical study in patients with early non-small cell lung cancer who have undergone surgical resection of the disease (patients with disease stage I-IIIA)
• More specifically, this clinical trial evaluates the effectiveness of adding an mRNA vaccine in combination with immunotherapy as a maintenance treatment after surgery or the completion of adjuvant chemotherapy, in order to minimize the possibility of disease resurgence in the future
• It is an mRNA vaccine that consists of a single synthetic mRNA that codes for up to 34 neo-antigens and is designed according to each patient’s genetic signature to increase the body’s immune system’s ability to detect and fight cancer cells

Not fully clarified aspects in the use of mRNA vaccines in lung cancer

• You should be aware that despite research in this specific therapeutic field in recent years, there is no approval for any mRNA vaccine in the prevention or treatment of non-small cell lung cancer
• mRNA vaccines are therapeutic agents under study, their effectiveness is not known and their administration cannot replace already existing approved effective treatments
• The safety of mRNA vaccines is not completely known as their widespread application against SARS-COV-2 infection in the pandemic period has taught us

In conclusion, mRNA vaccines appear to be an interesting more personalized anticancer approach in the prevention or treatment of cancer. However, we should know that it concerns scientific research or is still in early research stages. The evaluation of the efficacy and safety of mRNA vaccines should be further investigated through the conduct of more advanced clinical studies (Phase II and III). The inclusion of patients in clinical studies should be encouraged, but in any case only after proper scientific information.