TCR and micro RNA signatures of T cells for treating EBV-Lymphoma
Research type
Research Study
Full title
T cell receptor (TCR) and micro RNA signatures of T cells for treating Epstein Barr Virus (EBV)-driven lymphoma
IRAS ID
157162
Contact name
Jo CAMPBELL
Contact email
Sponsor organisation
SNBTS
Duration of Study in the UK
1 years, 11 months, 18 days
Research summary
Cytotoxic T Lymphocytes (CTL) can be used to treat post transplant lymphoproliferative disease (PTLD). PTLD is a serious side-effect of immune suppression following organ transplantation. The suppressed immune system fails to control latent Epstein Barr Virus (EBV). EBV transforms B cells into fast growing lymphoma cells and the disease has a high mortality rate. Our current CTL product has been used to treat >15 patients so far with a survival rate of over 60%. This is extremely encouraging, however, the current CTL product is difficult and laborious to make and relies on repeated stimulation of T cells with EBV virus-infected cells and uses medium supplemented with bovine serum. Removal of live virus and animal serum is desired to comply with future cell therapy regulations and to make the generation of CTL faster and more efficient. This new research proposal will re-generate lines using new GMP-compliant serum free media and peptide pools which should achieve the aim of making the process better and faster. To ensure that an improved product is truly as potent as the existing product, we need to generate new tools to analyse the content of the CTL lines - generation of microRNA signatures and sequencing of the T cell receptors in the CTL. The microRNA signatures of the CTL made with different methods will produce a “gold standard” screening signature for an effective line that has been successful in treating patients, and we can the compare the new lines against this to ensure that we have re-generated effective CTL. The receptor sequencing of existing and new lines will help us to assess the diversity of the anti-EBV specificity in the existing CTL and the new lines. Both of these may also be ultimately developed into tools to assess engraftment of the lines in patients.
REC name
Yorkshire & The Humber - South Yorkshire Research Ethics Committee
REC reference
14/YH/1323
Date of REC Opinion
24 Dec 2014
REC opinion
Favourable Opinion