With this therapy, which at another time was considered the stuff of science fiction, doctors were able to cure an aggressive and incurable type of blood cancer in several patients.
The treatment involves precisely editing the DNA of white blood cells to convert it into a “living drug” to fight cancer.
The first girl to receive the treatment, whose story we will publish in 2022, remains free of the disease and now plans to become a cancer researcher.
Currently, eight additional children and two adults with T-cell acute lymphoblastic leukemia have received the treatment, with a response rate of 64%.
T cells are considered the body’s sentinels and are responsible for detecting and destroying threats. However, with this type of leukemia they grow uncontrollably.
Chemotherapy and bone marrow transplants had failed. Aside from the experimental drug, participants in clinical trials had no other option than to make the dying process as bearable as possible.
“I really thought I was going to die and that I wouldn’t be able to grow up and do all the things that every child deserves,” says Alyssa Tapley, 16, from Leicester, central England.
He was the first person in the world to receive this treatment at Great Ormond Street Hospital and is now enjoying life.
The groundbreaking treatment, which took place three years ago, involved removing his old immune system and creating a new one. He spent four months in hospital and was unable to see his brother for fear of infection.
But now his cancer is undetectable and he only needs annual checkups. Alyssa is studying for high school, taking part in the Duke of Edinburgh Award, thinking about getting her driving license and planning her future.
“I am thinking about pursuing professional training in biomedical sciences and hope to one day also get into blood cancer research,” he said.
Innovative technology
The team from University College London (UCL) and Great Ormond Street Hospital used a technology called base editing.
The basics are the language of life. The four base types – adenine (A), cytosine (C), guanine (G) and thymine (T) – are the basic components of our genetic code.
Just as the letters of the alphabet form meaningful words, the billions of bases in our DNA form our body’s instruction manual.
By editing bases, scientists can access a specific part of the genetic code and change the molecular structure of a single base, converting it from one type to another to rewrite the instruction manual.
The researchers wanted to harness the natural power of healthy T cells to detect and destroy threats and use them against T-cell acute lymphoblastic leukemia.
This is a complex task. They had to genetically modify healthy T cells to attack cancer cells without making the treatment self-destructive.
The scientists started with healthy T cells from a donor and modified them.
The first genetic modification deactivated the attack mechanism of the T lymphocytes so that they could not attack the patient’s body.
The second step eliminated a chemical marker called CD7, which is present on all T lymphocytes. Eliminating them is essential to prevent the therapy from destroying itself.
The third modification was a kind of “invisibility cloak” that prevented the cells from being destroyed by a chemotherapy drug.
In the final phase of genetic modification, the T cells were instructed to look for cells with the CD7 mark.
Now the modified T cells would destroy any other T cells they encountered, whether cancerous or healthy, but they would not attack each other.
The therapy is given to patients and if no cancer is found after four weeks, they undergo a bone marrow transplant to regenerate their immune system.
“A few years ago this would have been science fiction,” says Professor Waseem Qasim from UCL and Great Ormond Street Hospital.
“We basically have to dismantle the entire immune system,” he added. “It is a deep and intensive treatment that demands a lot from patients, but when it works, it works very well.”
The study, published in the New England Journal of Medicinepresents the results of the first 11 patients treated at Great Ormond Street and King’s College Hospitals.
Nine of them achieved complete remission, which allowed them to undergo a bone marrow transplant.
Seven remain disease-free between three months and three years after treatment.
One of the biggest treatment risks are infections in those with weakened immune systems.
In two cases, the cancer cells lost their CD7 markers, allowing them to evade treatment and reappear in the body.
“Given the aggressiveness of this particular form of leukemia, these clinical results are truly remarkable,” said Dr. Robert Chiesa from the Bone Marrow Transplant Unit at Great Ormond Street Hospital.
“Of course, I am very happy that we were able to give patients hope that they would otherwise have lost.”
Dr. Deborah Yallop, consultant haematologist at King’s College Hospital, said: “We have seen impressive responses in eliminating leukemia that seemed incurable – it is a very effective approach.”
Commenting on the research, Tania Dexter, a doctor at UK stem cell charity Anthony Nolan, said: “Given that these patients had a slim chance of survival before the study, these results provide hope that treatments like these will continue to advance and become available to more patients.”
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