CAR-T 与 GvHD：我们是否已将 GvHD 从异体 CAR-T 治疗中工程化去除？

Autologous chimeric antigen receptor T cell (CAR-T) has transformed lymphoma therapy, but 40% to 60% of patients still relapse, and manufacturing is slow/expensive. Allogeneic CAR-T cells (from healthy donors or iPSCs) could overcome these issues. They can avoid patient leukapheresis and reliance on heavily pretreated autologous T cells, reduce the need for bridging therapy, permit advance manufacture, and allow deliberate donor and cell-subset selection.

However, they face two main immunologic barriers: (1) graft-versus-host disease (GvHD), in which donor T cells' native T-cell receptors (TCRs) may recognize patient tissues as foreign, causing acute/chronic GvHD; and (2) host-versus-graft rejection, in which the patient's immune system may reject the donor cells. In mismatched stem cell transplant (alloHCT), GvHD occurs in 50% to 80% of cases without intervention. By analogy, unmodified donor T cells with CARs might similarly attack HLA-mismatched host tissues.

Thus, successful allogeneic CAR-T must reduce donor-to-host alloreactivity while managing the distinct host-versus-graft barrier. This focused Perspective asks whether GvHD directed engineering has made clinically significant product-associated GvHD rare.