Gene editing is one of the most exciting areas of biomedical science and could have a major impact on how patients are treated for disease in the near future. A number of different gene editing methods have been developed, and while some – CRISPR-Cas9 for example – are just starting to be used in clinical trials, other techniques have now started to be used in clinical applications.
One such area where gene editing has started to be used is the treatment of leukemia. Leukemia is a group of cancers that arise in bone marrow where white blood cells are produced. The condition results in large numbers of underdeveloped or abnormal blastocytes being formed.
While leukemia can be managed in many cases, there is only a 57% survival rate in adults and the survival rate in children under 15 year of age is between 60% and 85%. Treatment involves radiation therapy, chemotherapy, or bone marrow transplants; however, recently researchers have focused on biotechnological methods to treat the disease.
Techniques such as CRISPR-Cas9 are attracting considerable interest, although the technique recently used to treat two leukemia patients involved transcription activator-like effector nuclease (TALEN) editing.
T-cells are vital in the immune response. The cells circulate around the body looking for foreign cells, which are identified by antigens on the outside of the cells. However, T-cells will not attack cells produced by the body, which means cancer cells are not attacked.
Malignant blastocytes have a unique antigen called CD19. While those cells will not normally be attacked by the T-cells, it is possible to genetically modify T-cells so they recognize the CD19 antigen as foreign.
To do this, T-cells need to be taken from a patient, be genetically modified, then reintroduced. Therapies with genetically engineered T-cells have proven to be effective and result in approximately half of patients going into remission.
However, since T-cells must be harvested, modified, and reintroduced, the process takes time and is expensive. Furthermore, the technique is not without its risks. Patients may develop cytokine release syndrome following the reintroduction of the modified T-cells. The condition can prove fatal.
In the recent trial, TALEN was used on T-cells that were obtained from non-HLA match donors. The gene editing technique was used to disrupt the CD52 receptor on the cells. With this technique, cells did not need to be taken from the patients.
After patients are treated with immunodepletion chemotherapy targeting their own T-cells, the TALEN edited cells were introduced. Since the patients’ T-cells have been reduced in number, this reduces the probability that the TALEN-edited cells will trigger an immune response.
Since the TALEN-edited T-cells do not have HLA antigens, they are not attacked and target the malignant blastocytes. In the trial on two patients, there was some rejection and associated side effects as not all of the HLA antigens were removed, although those side effects were able to be managed and the treatment was effective.
This successful trial showed how it is possible to modify T-cells obtained from sources other than the patient, speeding up the process and greatly reducing the cost. The technique also paves the way for future gene-editing therapies using cells from a universal donor.