6th November 2023
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Recently, there has been a revolutionary breakthrough in cancer research and treatment. A vaccine for Lung Cancer is being developed by the University of Oxford, University College London and the Francis Crick institute. It’s funded by Cancer Research and CRIS cancer foundation; they have invested £2.06 million. Lung cancer is still the leading cause of death, accounting for around 20% of cancer deaths every year. Only 1/10 people diagnosed with survive for more than 10 years, showing the limited success current treatments have.
What are current treatments?
Currently, treatments for Non-small cell lung Cancer (stage IA/B) involve primary surgery and then diligent surveillance imaging. Clearly, this is after the cancer has reached aggressive stages post diagnosis. Furthermore, out of patients with stage I disease, 25-30% of them have recurrences or new primary cancers occurring within 5 years. Another issue is that the post cancer treatments are very broad and target multiple cancerous pathways. As a result, there are many more side effects and excruciating monitoring is needed.
What are cancer’s mechanisms of infection?
Cancer refers to the uncontrolled division of abnormal, genetically mutated cells. Genetic mutations can be inherited or can happen spontaneously. These form tumours and metastasise to spread systemically- into the blood stream and to other organs. Cancer evades the immune system by presenting ‘self’ antigens: cell surface components that the body recognises as its own therefore doesn’t attack. A common form of cancer is carcinomas which form in epithelial tissue: tissue that covers all surfaces of cells. Some cancer cells also produce neoantigens which are abnormal cell surface proteins that arise from genetic mutations. However, there are many variants of them and usually not enough of one subtype in an individual to elicit an immune response.
What is this vaccine targeting and why?
The vaccine is more specifically targeting non- small cell lung cancer (NSCLC), which is a particularly aggressive form of lung cancer. It spreads through a multitude of methods: local invasion; spreading from lungs to lymph nodes through lymphatic vessels; haematogenous spread which is through the blood stream. NSCLC is so common due to a multitude of factors: carcinogens, lung exposure to the environment, ageing population and genetics. When I say lung exposure, I mean that the lungs have direct contact with pollutants from the environment, have a large surface area and lots of blood flow.
NSCLC has a very high mutation rate (changes in DNA sequences) in proteins involved in cell growth, survival and ability to metastasise- improving its ability to reproduce and spread. This also applies to adaptations to cancer treatments: proved in cancer’s ability to evade treatment. Furthermore, this form of cancer often causes no symptoms until its advanced: lung tissue has no pain receptors and tumours grow silently in peripheral lung areas.
What does this vaccine encompass?
The vaccine aims to prepare the immune system, before it’s overwhelmed, to recognise the abnormal cells that will potentially become cancerous. As I mentioned, NSCLC cells present neoantigens on their surface which are identified as foreign: these are the target for this vaccine. The mechanism is very similar to the AstraZeneca COVID-19 vaccine. Specific mRNA is produced in a lab which encodes for neoantigens. The mRNA is then delivered via ChAdOx2: a viral vector.
How does the body respond to the vaccine?
Body cells, specifically dendritic cells, take up the mRNA/viral vector complex and translate the mRNA into a protein: the neoantigen. They express the neoantigen on their surface via MHC class I/II which activate CD4+ and CD8+ cells. They are types of T cells which drive the immune response to cancer cells. For long term protection, memory leukocytes (T and B cells) will stay in the lungs and will patrol for any signs of neoantigens. Along with cytokine-induced NK cells and macrophages, this will allow a fast, strong immune response if they are detected.
What is the process of testing this vaccine?
Phase 1 trials will begin in summer 2026 and it is a 4-year process. A small group of people who have already been treated for early-stage Lung Cancer but have a high risk of it returning, will be first in the clinical trials. Phase 1 trials encompass determining the optimal dose for effectiveness and a minimisation of side effects. If these trials are successful, a wider cohort of people will be treated and hopefully yield successful results.
Hopefully, this breakthrough will save thousands, if not millions, of lives and will provide a baseline starting point for other preventative vaccines in the future. Cancer research UK and scientific researchers are working to prevent the multitude of grief that results from cancer worldwide.
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