The story so far: Scientists in the United Kingdom testing a new form of cancer therapy, reported success in a teenaged girl, Alyssia, with a form of cancer called T-cell acute lymphoblastic leukaemia.
In this form of blood cancer, the T-cells, which are a class of white blood cells, equipped to hunt and neutralise threats to the body, turn against the body and end up destroying healthy cells that normally help with immunity. The disease is rapid and progressive and is usually treated by chemotherapy and radiation therapy.
The BBC reported that Alyssia, 13, tried several of the standard treatments including chemotherapy and radiation but with limited success. Just when it seemed there was no hope, she was enrolled in the trial testing of an experimental medicine. This trial was led by doctors and scientists at the University College, London and Great Ormond Street hospital. Alyssia was the first to receive experimental gene therapy that relied on a new technique called ‘base editing.’
A person’s genetic code is several permutations of four bases: Adenine (A), Guanin (G), cytosine (C) and thymine (T). Sequences of these bases, akin to letters in the alphabet, spell out genes that are instructions to produce the wide array of proteins necessary for the body’s functions. In Alyssia’s case, her T-cells — perhaps because of a mis-arrangement in the sequence of bases — had become cancerous. A way to correct this mis-arrangement could mean a healthier immune system. In the last two decades, the world of biomedical engineering has been enthused by a technique that allow genes to be altered and errors ‘fixed.’ The most popular among these approaches has been the CRISPR-cas9 system.
Inspired by how certain bacteria defend themselves against viruses, by snipping out and storing pieces of their genes, the CRISPR-cas 9 system, consists of an enzyme that acts like molecular scissors. It can be made to cut a piece of DNA at a precise location and a guide RNA can be used to insert a changed genetic code at the sites of incision. While there are a few ways to effect such changes, the CRISPR-cas9 system is believed to be the fast, most versatile system to effect such gene editing. David Liu, of the Broad Institute, Massachusetts has improvised on the CRISPR-cas9 system to be able to directly change certain bases: thus, a C can be changed into a G and T into an A.
While still a nascent technology, base editing is reportedly more effective at treating blood disorders which are caused by so-called single point mutations, or when a change in a single base pair can cause terminal disease.
The objective of the gene therapy in the case of T-cell leukamia was to fix her immune system in a way that it stops making cancerous T-cells. First, healthy T-cells were extracted from a donor and put through a series of edits. The first base edit blocked the T-cells targeting mechanism so it would cease attacking Alyssa’s body, the second removed a chemical marking, called CD7, which is on all T-cells and the third prevented the cells being killed by a chemotherapy drug. Finally, the T-cells were programmed to destroy all cells — cancerous or protective — with CD7 marked on it. After spending a month in remission, she was given a second donor transplant to regrow her immune system that would contain healthy T-cells.
Three months after the treatment, her cancer seemed to resurface but the most recent investigations suggest no signs of it, according to the BBC. Alyssia was one of 10 people enrolled in the trial to receive the treatment.
It has been 1.5 years since she was first diagnosed with the disease and whether the treatment has reliably and entirely fixed her immune system, remains to be established.