公开(公告)号：US20240082305A1

公开(公告)日：2024-03-14

申请号：US18262303

申请日：2022-01-20

申请人： Seoul National University R&DB Foundation ,  Seoul National University Hospital ,  The Asan Foundation

发明人： Jaeseok YANG ,  Sun-Kyung LEE ,  Joon Young JANG ,  Junho CHUNG ,  Jerome HAN ,  Nara SHIN ,  Hyori KIM

IPC分类号： A61K35/17 ,  A61K39/00 ,  A61P37/06 ,  C07K16/28 ,  C12N5/0783

CPC分类号： A61K35/17 ,  A61K39/4611 ,  A61K39/4631 ,  A61K39/46433 ,  A61P37/06 ,  C07K16/2833 ,  C12N5/0637 ,  A61K2239/13 ,  A61K2239/17 ,  A61K2239/21

摘要： Antibody-mediated rejection (ABMR) is one of the main obstacles to successful transplantation, including ABO blood group-incompatible (ABOi) transplantation. C4d deposition is a marker of ABMR and is also found in most ABOi allograft tissues. Described herein are anti-C4d CAR Tregs that suppress ABMR in ABOi allografts. Anti-C4d CAR Tregs prepared by retroviral transduction of CAR into CD62L +CD4 +CD25 +Tregs, expressed Foxp3, CD25, CTLA-4, LAP, and GITR to similar extents as non-transduced Tregs. Anti-C4d CAR Tregs were activated by specific binding to C4d and suppressed in vitro T cell proliferation as well as non-transduced Tregs. Furthermore, adoptive transfer of anti-C4d CAR Tregs significantly prolonged mouse ABOi heart allograft survival (P