What is Gene Therapy? 

Gene therapy can be defined as the treatment of disease by the modification of a patient’s genes, by the transfer of genetic material into cells.^1,2 Gene therapy is a novel treatment approach, with clinical trials in infectious diseases, CNS and cardiovascular diseases, but mainly for the treatment of cancer.³

Since cancer is caused by changes in DNA, scientists have been searching for a way to correct those changes by using gene therapy to manipulate the DNA.⁴

There is a large need for advancing research into cancer treatments since most cancers currently have no curative treatment, and current treatments such as chemotherapy and radiotherapy often have many negative side effects; for example, the toxicity of chemotherapy regiments results in nausea, mouth ulcerations and mild cognitive impairments.⁵

Gene therapy offers the potential of new treatments for various types of cancer, with less systemic side effects and higher clinical efficacy.⁵

How does gene therapy work?

Genes, encoded within DNA, contain information to make proteins, which then control many important functions in the cell, such as cell division, growth and repair.⁵ Genetic mutations, which are alterations to the DNA sequence, can result in changes to protein function, structure or the amount of protein and, hence, can cause healthy cells to become cancerous. For example, a mutation could reduce or intensify a specific protein’s function, resulting in uncontrolled cell division, a feature of cancerous cells.⁵

Most cancers are caused by genetic faults developed throughout our lifetime, or faulty genes can be inherited. Genetic faults or mutations increase the risk of developing different cancer types. It is important to note that having a faulty gene doesn’t mean you will definitely develop cancer, it just increases your risk, called a genetic predisposition.⁶

Random genetic mistakes can develop in our genome throughout our lifetime, typically when cells are dividing or when exposed to a carcinogen, a substance such as cigarette smoke, which can result in cancerous mutations. It is also possible to inherit cancer gene faults from your parents.⁶

Using Gene Therapy to Treat Cancer 

• To replace missing or faulty genes: e.g. p53 is a tumour suppressor gene – which is essential in working to prevent or stop tumours from forming in a healthy cell. However, if cells are missing this gene or aren’t working correctly, the cell can be fixed by adding working p53 copies into the cell
• To prevent the spread of cancer (metastasis): ‘oncogenes’ are genes that cause new cancer or the spread of an existing cancer. These genes could be stopped by gene therapy
• Utilising the body’s immune system: inserting genes into cancer cells to trigger the body to recognise and attack the cancer cells as foreign invaders
• To enhance chemotherapy, radiotherapy or hormone therapy: genes could be inserted into cancer cells to allow other treatments to kill the cells more easily
• To kill the cancer cells directly: create ‘suicide genes’ that enter cancer cells, and cause them to die.
• Preventing blood flow to the tumour: blood supply is essential for tumours to grow and survive, so preventing blood flow can kill the tumour
• Protect healthy cells: Gene therapy could protect healthy cells, allowing higher doses of chemo or radiotherapy without as many side effects⁷

Types of Gene Therapy

Somatic versus Germline Gene Therapy

• Somatic Gene Therapy: modifies the genetic material of somatic cells, which are the non-reproductive cells (all cells in the body except sperm and egg). This means alterations are not transferred to offspring⁸
• Germline Gene Therapy: modifies the genetic material of germ cells, which refers to sperm and egg cells. This means that the alterations are passed onto offspring and it could potentially remove hereditary disorders from a family line. Germline gene therapy is not yet used in humans, as it has additional ethical considerations since it affects future generations⁸

Current Gene Therapy Methods for Cancer

Viral Vectors: using viruses to deliver therapeutic genes

A virus can be used as a ‘vector’ to deliver genetic material into a cell.⁹ They can be changed or ‘deactivated’ in a laboratory so that they no longer cause disease when introduced into patients.⁷

Often, cells are taken from the patient and mixed with the virus in a lab, allowing the virus with the desired therapeutic gene to find its way into cells. The cells are then grown in a lab and reintroduced into the patient by intravenous infusion into the vein or injection into the tumour.⁷ Otherwise, the vector with the attached gene is directly inserted into the patient by intravenous infusion or injection into a tumour. Once the gene reaches the cell, it mixes with the human genetic material and needs to be turned on to produce the protein of that gene.

In cancer vaccines, viral vectors can deliver specific cancer-related antigens into the body, stimulating the immune system to recognise and kill any cancer cells.⁹

Non-Viral Methods

Liposomes

Liposomes are tiny, fat-like particles made in laboratories. They can contain drugs or other cancer therapeutics and result in fewer side-effects than when drugs are delivered alone. Liposomes are a promising nonviral vector for gene delivery! 

CRISPR-Cas9

CRISPR-Cas9 refers to a laboratory tool that can be used to change or edit pieces of a cell’s DNA. It can be thought of as a pair of scissors that can alter DNA in a very precise way. It is a beneficial method as it is easily customisable, allowing editing of almost any segment within of DNA within the human genome, and is much faster and more precise than many other genome editing methods.^3,4

For example, CAR-T cell therapy which changes the genes in T-cells to fight cancer.³

Kymriah is a successful CAR-T therapy that can be used to treat cancer in children and young adults. It involves genetic modification of patients’ immune cells to recognise and attack cancer cells. This drug has been found to be highly effective in treating patients with relapsed or refractory leukemia and was approved by the FDA in 2017.³

Benefits of Gene Therapy for Cancer Treatment

Gene therapy has the potential to cure or significantly improve the lives of patients with difficult to treat or incurable cancers.³

The benefits of gene therapy over other treatment approaches include:

• Targeted approach: reducing off-target negative side effects, minimising damage to healthy cells
• Long-term potential: has the potential to provide treatments with higher long-term efficacy by correcting genetic defects, rather than relapse, which often occurs with current treatments
• Personalised medicine: all cancer patients are different and have different causes, and gene therapy can be modified to be unique to each individual patient, hopefully providing more effective treatment

Challenges or Limitations to Gene Therapy for Cancer Treatment

• Delivery: It is important to deliver genes precisely to cancer cells to prevent damaging healthy cells and off-target effects⁴
• Immune response: the body may attack the therapy, especially if it is a viral vector, as the body may recognise it as foreign
• ‘Off-target’ editing: where CRISPR cuts DNA outside of the target gene, can be harmful and can potentially turn healthy cells cancerous⁴
• Cost and accessibility: Gene therapy is expensive and not yet widely available
• Side effects: Potential unintended genetic changes could occur, or new harmful mutations may be introduced that could harm the patient

With lots of current research going into gene therapy for the treatment of cancer, these current challenges will hopefully be resolved by improving delivery methods, minimising risk and reducing the cost of the treatment. 

Frequently Asked Questions

How soon will gene therapy be available for most cancers?

The FDA (US Food and Drug Administration) has currently approved 36 gene therapies, but many more are in development. It is predicted that 10-20 new gene therapies will be approved each year by 2025. ¹⁰

However, it is important to note that gene therapy is still a relatively novel therapy and isn’t yet at the level of replacing conventional therapies such as chemotherapy, radiotherapy and surgery. 

Is gene therapy safe?

Since gene therapy is relatively new, some risks may be unpredictable. This is why medical researchers and institutions are working hard to ensure that clinical trials and approved treatments are as safe as possible by looking through to minimise any possible risks. 

Will gene therapy cure cancer completely? 

Gene therapy is not guaranteed to cure cancer completely, but it is a new and potentially curative approach to treating cancer. It is important to remember there is still lots more to learn and discover, but gene therapy does offer an exciting new avenue for treatments.