This post was originally published on here
Can you imagine a greater boon than finding a cure for an incurable form of cancer? Scientists from University College London (UCL) and Great Ormond Street Hospital (GOSH) have found a cure for a form of blood cancer that was previously “incurable”.
T-cell acute lymphoblastic leukaemia (T-ALL), which mostly affects children and young adults, is characterised by the abnormal and uncontrollable growth of white blood cells in the bone marrow and blood.
advertisement
Traditional treatments for cancer include CAR-T (Chimeric Antigen Receptor T-cell) therapy, wherein healthy T-cells are used to kill cancer cells. Similar to a mythological chimera, which is a mashup of different kinds of animals, a chimeric antigen receptor (CAR) is a combination of different kinds of protein machinery that can do multiple jobs at once.
The drawback of CAR-T therapy in T-ALL is that it targets healthy T-cells as well, because the cancer affects the same white blood cells meant to counteract infections.
HOW DNA BASE EDITING CAN BE A BOON FOR CANCER PATIENTS
To prevent this, the researchers used a technique called base editing, which is a precise form of CRISPR-Cas9 technology that changes single DNA letters without cutting the strand.
Published in the New England Journal of Medicine, the research marks the first-ever use of base-edited CAR-T cells in humans.
As part of the study, the researchers made four DNA edits.
First, they removed the TCR (T-cell receptor) from the donor cells. These are identity tags on T-cells that help them recognise enemies such as antigens.
Removing the TCR is necessary to prevent the rejection of donor cells entering the patient’s body as part of immunotherapy.
For the same reason, the researchers also removed the HLA (human leukocyte antigen), which are proteins on cells serving as a name tag for the immune system. Since donor cells with a different HLA can be rejected by the body, base editing removes the HLA, making them “universal” and safe for any patient.
Second, the scientists removed the CD7 protein from the donor cells. This protein is found on the surface of normal T-cells and most T-ALL cancer cells. This way, the therapy will only target the CD7 protein of cancerous T-cells and normal T-cells in the body, and not the donor T-cells.
Third, the team removed CD52, another surface protein on T-cells. The reason is to make the edited donor cells resistant to a drug called alemtuzumab, which is used to treat T-ALL patients. This is to ensure that the beneficial cells survive and the cancerous ones are destroyed.
Last, they added an anti-CD7 CAR, an artificial hunter protein, to the edited T-cells. This protein recognises CD7 on cancer cells, locks onto them, and triggers the edited donor T-cell to destroy the cancer cells.
The treatment begins with chemotherapy, which clears the patient’s immune cells. Then, the patient is infused with edited BE-CAR7 cells, which expand and wipe out all cells that are CD7-positive. After that, a stem cell transplant is performed to rebuild a healthy immune system.
The first phase of the study, conducted in 2022 on 11 patients, most of them children, saw 100 per cent of the participants reach initial remission. Of these, 82 per cent achieved deep or undetectable remission within four weeks and were eligible for a stem cell transplant. Around 64 per cent of the patients have remained cancer-free for a long time, including some being free of the disease for more than three years.
However, there are a few side effects, including an over-reaction of the immune system due to cytokine release, skin rashes, low blood cell counts, and a high risk of infections because the therapy kills all T-cells temporarily.
Alyssa, the first patient on whom this therapy was tested, has remained cancer-free since 2022. When she started the treatment at 13, she had exhausted all other options. Now 16, she is living a normal life.
Not only does the study offer real hope for “incurable” cases, but it also shows that “universal” cells could be faster and cheaper in future.
– Ends
Must Watch
