GAMECHANgER-1: Treg therapy to suppress memory responses to HLA
Research type
Research Study
Full title
ReGulatory T cells in highly sensitised pAtients to iMProvE outComes after HLA-Ab iNcompatiblE Renal transplantation (GAMECHANgER-1)
IRAS ID
1003748
Contact name
Alberto Sanchez-Fueyo
Contact email
Sponsor organisation
King’s College London
Eudract number
2021-001664-23
ISRCTN Number
ISRCTN14582152
Research summary
Kidney transplantation is the best treatment for patients with kidney failure. Donor organs are allocated using various criteria, one of which is the presence of antibodies (Ab) against tissue antigens called HLA, which indicate whether potential recipients will mount an aggressive rejection response against a particular donor. Organs are not offered if any of the Ab react against a prospective donor so dialysis patients with multiple Abs (~1/3rd on the transplant list) can wait a long time for a suitable donor. Although specialised treatment to allow Ab to be ignored in the allocation process is sometimes available, more powerful drugs to suppress the immune system must be used and patients still suffer high rates of rejection. This study will test a new personalised approach to improve outcomes for this group with multiple Ab, using the patient's own specialised white blood cells with natural suppressive properties (called 'regulatory T cells' (Tregs)) that we will purify and grow-up in the laboratory before infusing them back into the patient. First, in Part 1, we will study the way cells from these patients respond to HLA proteins. If we see a specific pattern of response in at least 21 patients, we will invite these patients into Part 2, in the order in which they were identified. The first 9 patients will be asked to donate extra blood tests in Part 1, the results of which will allow us to interpret the overall results at the end. In stage 1 of part 2, Tregs will be administered to the first 12. After assessing the responses of these, we will then administer Tregs to the remaining 9 patients in stage 2. We will determine whether Tregs change the numbers and subtypes of Tregs circulating in the patients and suppress the responses of patient cells to HLA proteins. This study will inform us whether Tregs are capable of suppressing responses to HLA in dialysis patients with multiple Abs and thus is a potential strategy for testing in larger trials.
REC name
South Central - Oxford A Research Ethics Committee
REC reference
21/SC/0253
Date of REC Opinion
22 Nov 2021
REC opinion
Further Information Favourable Opinion