'Training' viruses to kill cancer

Great Ormond Street Hospital (GOSH) is to become the first hospital in the UK to offer a pioneering cancer therapy, known as CAR-T therapy, to NHS patients with an aggressive blood cancer called B-cell acute lymphoblastic leukaemia.

To understand how CAR-T cell therapy works, we caught up with Dr Sara Ghorashian, who as a Consultant Paediatric Haematologist and Lead for Cell Therapies at GOSH, is one of the few clinicians who has both made the cells in the lab and used them to treat patients.

“It's a super exciting time,” she enthused. “We've been delivering CAR-T therapies here at GOSH for many years – the first study, led by Professor Persis Amrolia, opened in 2012.”

Dr Ghorashian explained the basic concept of CAR-T cell therapy, which uses a patient’s own immune cells to fight leukaemia.

“Immune cells are specially adapted cells which help fight infections – the immune cells that we use for this are called T-cells and they normally fight viral infections. If you have a cold, they'll go into the tissues around your nose and help to mop up any cells that are infected by the cold virus. They're very good for that, but they're not great at doing the same for cancer, because they can't ‘see’ the cancer cells.

“The cancer looks like a normal cell and so they can't recognise it. We take the T-cells and we engineer them to recognise cancer cells. Then when we put them back into the patient, they will kill all the cells that they recognise as cancer cells.”

The first step, Dr Ghorashian explained, is to remove the immune cells from a patient’s blood.

“The immune cells are removed and everything else gets returned to the patient. Then we've got a bag at the end of the day that's got lots of immune cells in it, including lots of T-cells.”

The T-cells are carried to the laboratory, where once being activated, they are exposed to the new DNA, the code which will help them to spot leukaemia cells. The clinicians use an unlikely ally to transfer this DNA – a modified virus.

“We've completely disabled the virus,” Dr Ghorashian reassured. “It can't do anything else other than go into the cells, insert the gene that we want and then it just breaks up. The virus can't survive through this process, but it does the job and it puts in the gene that we want.

“After about a week of growing the cells in the lab, we have a relatively pure T-cell product which now has the capacity to recognise leukaemia.”

The re-coded T-cells are cleaned up and go through a quality control process before they’re given back to the patient.

“When the cells go back into the patient, they feel like they're back at home, because they've come from that patient. They start dividing and circulating around the body, and start to recognise the leukaemia and kill it.

“For patients who relapse post-transplant [bone marrow transplant, BMT], there isn't really another therapy option, particularly if they relapse early after transplant. This is a new avenue of treatment which offers a chance of therapy for patients who otherwise wouldn't have many good options.”

Finally Dr Sara Ghorashian explained that it’s on the basis of years of research that GOSH has been granted a license to provide CAR-T cell therapy.

“We've developed an international reputation in developing and delivering academic CAR-T cell studies. It's on the back of that experience and actually having treated patients since 2013 with CAR-T cells here, that we've been approved as a centre to now do it for licensed CAR-T cells. It's a very exciting time.”