About Phase 1 trial of T-cell therapy to prevent viral disease in children post transplant
For stem cell transplant recipients, graft-versus-host disease (GvHD) is a serious complication that can occur following transplantation. GvHD occurs when some of the immune cells (T cells) from the transplant attack the patient. If the level of tissue matching between the patient and donor is low, GvHD is more likley to occur.
When a patient is selected to receive a type of transplant called a haploidentical haematopoietic stem cell transplant (haplo-HSCT), which is not an ideal tissue match, most T cells are removed from the transplant to minimise the risk of GvHD.
As T cells are important for fighting viruses, removing them means that the transplant recipient is at higher risk of developing an infection. In this trial, we will test a new preventative T cell therapy for four common viruses. The therapy will be grown from the blood of the transplant donor and given to patients who have received a haplo-HSCT.
One aim of this trial is to see if this T cell therapy is safe for transplant patients. In addition, we would like to see if the T cells that we grow in the laboratory from the transplant donors can help to restore the recipients’ immune systems. This may help prevent infectious complications from developing.
In this trial, a T cell therapy targeting a number of viruses will be created for each paediatric patient. A blood sample from the stem cell transplant donor (a family member), collected prior to the transplant, will be used to grow these T cells. The patient will then receive their transplant, be given at least 4 weeks to recover, and then the T cell therapy will then be infused intravenously. They will receive six infusions at fortnightly intervals.
The main aim of this clinical trial is to see whether this new T cell therapy is safe for transplant recipients. In addition, we would like to see the effect of these cells when they are infused into transplant recipients who are at risk of uncontrolled viral infection.
The viruses we are targeting are Epstein–Barr virus, cytomegalovirus, BK virus and adenovirus. The T cell therapies that we grow will vary from donor to donor, as different people have different immune responses against these viruses.
Patients receiving this particular type of stem cell transplant* are at high risk of viral complications, either due to reactivation of a virus that they already have, or by acquiring a new virus while their immune system is regenerating from the transplanted stem cells. This is because the donor’s immune cells (T cells and B cells) are removed from the stem cells before they are given to the patient. This is done to reduce the risk of graft-versus-host disease, as the transplant is not an ideal tissue match in these cases. Our trial is a prophylactic design, aiming to prevent viral complications during the critical time period post-transplant when the patients are most at risk. By infusing T cells that are primed to recognise four common viruses, we hope to bridge the gap while their own immunity ‘reconstitutes’.
If an existing viral infection (e.g. cytomegalovirus) that has been lying dormant reactivates while the infused T cells are circulating, the T cells should kill the virus-infected cells. Similarly, if a new virus infects the patient, the T cells will kill the virus-infected cells and minimise the clinical complications that the patient will experience.
* T cell receptor αβ+/CD19+-depleted haploidentical haematopoietic stem cell transplant
Participation
Visit the Australian New Zealand Clinical Trials Registry for eligibilty criteria