In the battle against cancer, gene-editing could be a revolution

Alyssa, a teenage British patient, is giving hope to people suffering from the most aggressive strains of leukaemia

Technician holding a blood sample ready for testing with other human medical samples in the background. Getty Images
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The story of Alyssa, the cancer survivor who experienced a breakthrough from a new DNA-editing therapy, has inspired patients and doctors treating cancer worldwide. Alyssa, 13, has been battling acute lymphocytic leukaemia since May 2021. Although this cancer can affect both adults and children, cases in children are highly curable with chemotherapy. Still, unfortunately, several patients will have a recurrence and have low chances of survival due to the aggressive nature of this leukaemia.

While treatment options for this disease include bone marrow transplantation, in Alyssa's case, this also failed. When you reach this point, the treatment options are limited to palliative care that focuses on alleviating the symptoms of the patient who will eventually die from the disease. However, Alyssa and her family decided to try a new experimental treatment never used for such a case before.

They opted for the therapy that uses a new technology known as Clustered Regularly Interspaced Short Palindromic Repeats – commonly known as Crispr. This technology recognises the defect in the DNA. Then it repairs the codon, a sequence of three nucleotides forming a unit of genetic code in a DNA or RNA molecule, which controls or causes cancer. It can also modify the codon with the same technique as other cells so that they can fight against cancer. Many ongoing clinical trials are evaluating the efficacy of this gene-editing tool, which was introduced only about six years ago.

Researchers are studying how Crispr could be used to fight cancer. AP

Last year, a team of oncologists, including myself, published a scientific paper about this technique, as we believed it would have the potential to cure cancers in the future despite all the challenges the technique still has. In Alyssa's case, her T cells – usually a tool for the immune system to fight against invaders into the human body and protect from diseases – became the source of the cancer cells. These cancer cells started to attack her body and her normal cells. Despite chemotherapy and bone marrow transplant treatments, her T cells continued to grow out of control, causing her cancer to spread more aggressively. After her T cells were modified using the Crispr technique, the team at the Great Ormond Street Hospital in London infused them back into her body, unleashing a new army of healthy T cells that started to attack the cancerous T cells.

To the team's surprise, the newly engineered T cells were able to eliminate all the cancerous T cells. The next step was restoring her immune system through another bone marrow transplantation. Bone marrow transplantation carries a very high risk of infection-related complications, given that the body of a patient like Alyssa has no immunity against viruses or bacteria. Hence, she was isolated for almost three months from her brother, who was attending school, and was under stringent medical supervision to monitor her critical condition.

Alyssa eventually pulled through this difficult time and returned home with no signs of cancer and a fully functional immune system. Her journey was undoubtedly challenging and not easy, but she was brave enough to go through this experimental treatment without knowing its outcome. Alyssa's battle is not over, and she needs to continue to be under close follow-up as the risk of cancer recurrence is always there.

But her story is about the success of science and the courage of this brave teenager and her family. Our ongoing work to understand how cancer is growing and trying to target these pathways with novel therapies continues to advance as more breakthroughs are happening. Other promising technologies that are evolving, and used nowadays for cancer treatment, include blood-based DNA screening for cancer, such as the Galleri Test and CancerSEEK. Such tests have more public uptake and will make cancer screening easier by covering many cancers for which we previously didn't have screening. Another tool that we use in our clinic daily is measuring circulating tumour DNA, which helps detect cancer recurrence earlier than waiting for the cancer cells to grow and show on scans such as CT or MRI.

The Zayed Centre for Research into Rare Disease in Children at Great Ormond Street Hospital in London is helping to advance cancer treatment. Ministry of Presidential Affairs

Cancer, described for the first time in ancient Egypt more than 5,000 years ago, remains a significant health challenge and continues to be a global cause of death in both developing and developed countries. As we advance our tools to treat cancer, we must ensure that all patients from different backgrounds and economic statuses have access to treatment. Alyssa's story marks the beginning of a new era of gene-editing to try to cure cancer. Her story also highlights how important it is for patients with cancer to accept being treated in clinical trials. The participation and courage of patients and their families to confront uncertainties are commendable.

Precision medicine, through which patients are treated based on the genetic make-up of their disease, is becoming a new standard for a number of diseases, including cancer. Many approved drugs target specific mutations, but Alyssa's is the first successful case of human gene-editing for acute lymphocytic leukaemia.

There are also some setbacks with gene-editing, like off-targets wherein unintended modification of normal genes could cause side effects. Also, the effect of gene-editing might not be permanent and could be reversed, leading to the cancer cells getting active again. Such uncertainties are why more research and longer follow-ups for these cases after the gene-editing procedure are needed.

Ultimately, Alyssa's story sheds light on a new era of cancer research and potential cure. We are fortunate to witness such progress, and we are optimistic about more success stories using a number of new technologies at our disposal today, including Crispr.

Published: December 23, 2022, 6:00 PM