A federal advisory committee of US National Institutes of Health has approved a proposal for using the CRISPR CAS-9 genome editing tool in clinical trials on humans.
The proposal is to test the treatment of cancer by picking out T-cells, which are a special type of immune cells found in the body, from patients with cancer and to modify the T-cells and use them to target the cancer cells. This information was published online in a report in Nature , on June 22.
The proposed study is led by Edward Stadtmauer, a physician at University of Pennsylvania. As per the proposal, the university will manufacture the edited cells and recruit patients for the trial. The Recombinant DNA Research Advisory Committee, which advises the NIH director on basic and clinical research, reviews all proposals for human trials that involve modification of the DNA. Its approval is a major step forward for any proposed trial. The team will now have to convince regulators in the U.S. and their own institutions to allow the trial which is expected to start by the end of the year.
The procedure involves the use of modified T-cells to target and kill the cancer cells. T-cells are part of the body’s immune system, assisting in cell-mediated immunity. In the test, T-cells from the patient will be taken out and modified using the CRISPR gene editing tool and then reinserted into the body, where they will perform the required function.
CRISPR, the acronym of Clustered regularly interspaced short palindromic repeats, are segments of prokaryotic DNA containing short repetitions of base sequences.
While it is a promising technique, it has to be handled carefully as tampering with the immune system is a delicate process. “It has to be made sure that the manipulated cell will retain the memory of the modification and continue to work as required. Also it should not trigger off unexpected things, such as autoimmune disorders,” said Dr C.S. Mani, Surgical Oncologist with the Madras Cancer Care Foundation and Cancer Research and Relief Trust, Chennai. So, the first thing to test is whether CRISPR is safe to use with humans, and a small initial trial will test this.
In the proposed procedure, taking out T-cells from 18 people with different types of cancer, and the researchers will modify them in three specific ways. First, insert a gene associated with a protein which will detect the cancer cells and direct the T-cell to target them. Second, knock off a naturally occurring gene in the T-cell which can hinder this. Lastly, remove a gene which codes for a protein that identifies the T-cell as an immune cell – this can prevent the cancer cell from disabling the T-cell. These edited T-cells will be infused into the cancer patient, where they will get to work on the cancer cells.
“Cancer thrives by evading the immune system. A branch of therapy involves activating the immune cells because a mutation prevents immune cells from recognising cancer cells. This was a breakthrough made in 2013. CRISPR is a highly efficient tool which helps in very precise editing of the genes.” added Dr Mani.
