TY - JOUR
T1 - Chimeric HLA antibody receptor T cell therapy for humoral transplant rejection
AU - Arana, Carolt
AU - Garcia-Busquets, Ainhoa
AU - Nicoli, Michael
AU - Betriu, Sergi
AU - Gille, Ilse
AU - Heemskerk, Mirjam H M
AU - Heidt, Sebastiaan
AU - Palou, Eduard
AU - Rovira, Jordi
AU - Diekmann, Fritz
N1 - Publisher Copyright:
© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.
PY - 2024/12/20
Y1 - 2024/12/20
N2 - Antibody-mediated rejection (ABMR) is a significant obstacle to achieving optimal long-term outcomes after solid organ transplantation. The presence of donor-specific antibodies (DSAs), particularly against human leucocyte antigen (HLA), increases the risk of allograft rejection and subsequent graft loss. No effective treatment for ABMR currently exists, warranting novel approaches to target the HLA-specific humoral alloimmune response. Cellular therapies may hold promise to this end. According to publicly available sources as of now, three independent laboratories have genetically engineered a chimeric HLA antibody receptor (CHAR) and transduced it into human T cells, based on the demonstrated efficacy of chimeric antigen receptor T cell therapies in malignancies. These CHAR-T cells are designed to exclusively eliminate B cells that produce donor-specific HLA antibodies, which form the cornerstone of ABMR. CHAR technology generates potent and functional human cytotoxic T cells to target alloreactive HLA-specific B cells, sparing B cells with other specificities. Thus CHAR technology may be used as a selective desensitization protocol and to treat ABMR after solid organ transplantation.
AB - Antibody-mediated rejection (ABMR) is a significant obstacle to achieving optimal long-term outcomes after solid organ transplantation. The presence of donor-specific antibodies (DSAs), particularly against human leucocyte antigen (HLA), increases the risk of allograft rejection and subsequent graft loss. No effective treatment for ABMR currently exists, warranting novel approaches to target the HLA-specific humoral alloimmune response. Cellular therapies may hold promise to this end. According to publicly available sources as of now, three independent laboratories have genetically engineered a chimeric HLA antibody receptor (CHAR) and transduced it into human T cells, based on the demonstrated efficacy of chimeric antigen receptor T cell therapies in malignancies. These CHAR-T cells are designed to exclusively eliminate B cells that produce donor-specific HLA antibodies, which form the cornerstone of ABMR. CHAR technology generates potent and functional human cytotoxic T cells to target alloreactive HLA-specific B cells, sparing B cells with other specificities. Thus CHAR technology may be used as a selective desensitization protocol and to treat ABMR after solid organ transplantation.
UR - http://www.scopus.com/inward/record.url?scp=85213596539&partnerID=8YFLogxK
U2 - 10.1093/ndt/gfae160
DO - 10.1093/ndt/gfae160
M3 - Article
C2 - 39025810
SN - 0931-0509
VL - 40
SP - 19
EP - 26
JO - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
IS - 1
ER -