On the journey to fight cancer, currently only 2 vaccines have been proven to directly prevent cancer. They are both targeted at cancers caused by specific viruses, namely the hepatitis B vaccine for preventing liver cancer caused by the hepatitis B virus, and the HPV vaccine for preventing cervical cancer caused by the human papillomavirus.

Lung cancer currently has the highest incidence and mortality rates of all cancers worldwide, and has always been a focus of medical research. If there were a vaccine that could prevent lung cancer with just one injection, once successfully developed, it would save numerous patients’ lives, undoubtedly making it a great breakthrough in medical history. This seemingly unattainable goal may soon become a reality.

1 New funding for world’s first lung cancer vaccine

On March 22, researchers from the University of Oxford, the Francis Crick Institute, and University College London have been granted £1.7 million (approximately 15.53 million RMB) of funding from the Cancer Research UK and the CRIS Cancer Foundation to develop a lung cancer vaccine. The team will receive funding over the next 2 years to support lab research and initial manufacturing of 3,000 doses of the vaccine at the Oxford Clinical BioManufacturing Facility.

This research complements existing efforts through lung health checks to detect lung cancer earlier in people who are at greatest risk. Professor of Experimental Oncology at the University of Oxford and founder of the LungVax project, Professor Sarah Blagden, said: “When given to people with cancer at its earliest stages, anti-cancer treatments are more likely to be successful. We are developing a vaccine to stop the formation of lung cancer in people at high risk. This is an important step forward in preventing this devastating disease.”

Chief Executive of Cancer Research UK, Michelle Mitchell, said: ‘The science that successfully steered the world out of the pandemic could soon be guiding us toward a future where people can live longer, better lives free from the fear of cancer.’ The technology used in LungVax is similar to the highly successful Oxford/AstraZeneca COVID-19 vaccine.

2 The Mystery of Cancer Prevention

Fig1:Mechanisms of action of vaccines,doi: 10.2147/IDR.S315727

COVID-19 is caused by a viral infection, while the factors of cancer are extremely complex. The key to applying COVID-19 vaccine technology to cancer vaccines lies in its working principle.

When affected by the novel coronavirus, vaccines generate an immune response by recognizing the spike protein. The Oxford University-developed COVID-19 vaccine is an adenovirus vector vaccine, which carries the DNA encoding the spike protein in a harmless adenovirus vector. Once the vector enters the body, our cells start expressing the spike protein, triggering the immune response to achieve a protective effect.

The difference between virus infection and cancer cells lies in the fact that cancer cells are mutations of the body's own tissue cells, rather than foreign invaders like viruses or bacteria. Therefore, how to identify and distinguish between normal cells and cancer cells in vivo, and launch targeted attacks against cancer cells, is a major challenge faced by the human immune system.

Lung cancer cells are different from normal cells due to carcinogenic mutations in the DNA of the cells. New antigens appear on the surface of the cells. The research team has discovered a new antigen on the surface of lung cancer cells - red flag. This new antigen is like the "ID card" of lung cancer cells, expressed only in lung cancer cells.

3 The Past and Present of Cancer Vaccines

It wasn't until the end of the 20th century that the idea of cancer vaccines truly took shape. During this period, with the development of immunotherapy and in-depth research in cancer immunology, people gradually understood that it is possible to identify and kill cancer cells by activating the immune system, which is also the mechanism of modern tumor immunotherapy.

3.1 Development of preventive cancer vaccines

As early as 2010, sipuleucel-T, an autologous immune cell therapy for prostate cancer, was the first vaccine approved by FDA for solid tumors. Research data shows that sipuleucel-T can extend survival by 4.1 months. However, the high cost of the vaccine and the complexity of its manufacturing process have limited its widespread use. Moreover, many cancer vaccines based on prostate-specific antigen (PSA) have shown low clinical response rates in Phase III studies.

In 2013, a series of phase III clinical trials for cancer vaccines targeting tumor-associated antigens (TAAs) failed to meet expectations. The key issue with TAAs as vaccine antigens is that they are not unique markers specific to tumor cells; they are also expressed in small amounts in normal cells. This poses significant risks in terms of immunogenicity and safety for TAA-based vaccines.

3.2 Advancements in therapeutic cancer vaccines

The goal of therapeutic cancer vaccines is to prolong the survival of cancer patients, prevent metastasis, recurrence, and death, and other adverse outcomes. In 2013, research on therapeutic cancer vaccines was recognized by Science as the most influential scientific breakthrough of the year. Following that, in 2017, personalized mRNA cancer vaccines entered human trials for the first time. Personalized cancer vaccines obtain cancer samples from patients, identify and select new antigens through genetic sequencing, and design vaccines based on this basis. In March 2024, a therapeutic vaccine targeting tumor-specific new antigens with cytotoxic T cell responses was published in Nature and is currently undergoing Phase I trials, representing one of the optimization directions for mRNA therapeutic vaccines.

According to statistics, there are more than 500 cancer vaccines currently under research globally, with 16 already approved and on the market, covering cancer types such as lung cancer, bladder tumors, melanoma, and glioblastoma.

The LungVax vaccine seems to be "old wine in a new bottle", using traditional adenovirus vectors combined with discovered DNA chains of new lung cancer antigens. This vaccine technology has already been validated for its preventive effects during the COVID-19 pandemic. If researchers can replicate such success, it will save the lives of numerous lung cancer patients.

The preventive cancer vaccine may probably lead us towards a future where we can live longer and better free from occurrence of cancer. The development of the LungVax vaccine has opened a new door for cancer treatment, and we hold it firmly that with the continuous advancement of future technology, cancer will no longer be an insurmountable obstacle.

References

[1]https://www.ox.ac.uk/news/2024-03-22-new-funding-development-worlds-first-lung-cancer-vaccine

[2]Mascellino MT, Di Timoteo F, De Angelis M, Oliva A. Overview of the Main Anti-SARS-CoV-2 Vaccines: Mechanism of Action, Efficacy and Safety. Infect Drug Resist. 2021 Aug 31;14:3459-3476. doi: 10.2147/IDR.S315727.

[3]https://www.fda.gov/media/78511/download

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[5]https://www.nature.com/articles/s41591-024-02851-9#Sec40

[6]Xie W, Chen B,Wong J. Evolution of the market for mRNA technology[J]. Nature reviews. Drugdiscovery, 2021, 20(10): 735-736.