Murine allogeneic CD19 CAR T cells harbor potent antileukemic activity but have the potential to mediate lethal GVHD

Abstract

Key Points Donor-derived allogeneic CAR T cells are functional and eradicate ALL. Allogeneic CD4+ CAR T cells can mediate acute GVHD but only when CD19+ leukemia is present.

Sequential allogeneic and autologous CAR-T–cell therapy to treat an immune-compromised leukemic patient

“…Allo-CAR-T may induce severe CRS or GVHD. 17 Citing safety issues from allo-CAR-T infusion because of severe adverse responses, the US Food and Drug Administration terminated 2 phase 1 "off the shelf" CAR-T (UCART123) trials sponsored by Cellectis. Rigorous donor selection or selection of virus-specific allogeneic T cells may reduce these side effects.…”

Treatment of solid tumors with chimeric antigen receptor-engineered T cells: current status and future prospects

“…Most EGFRvIII-redirected CAR-T studies were assessed in glioblastoma models. Early preclinical studies demonstrated the potential antitumor effect of first-generation CARs targeting EGFRvIII (González-Navajas et al, 2012;Jacoby et al, 2015). Subsequent second-and third-generation CAR-T cells validated their antitumor activity on EGFRvIII + glioblastoma cells.…”

Allogeneic CAR19 cells clear ALL

“…However, production of autologous CAR19 cells from these patients can be difficult as patients frequently have T-cell dysfunction, due to disease and/or treatment-related effects. In this issue of Blood, Jacoby et al 1 addressed this by exploring whether allogeneic donor CAR19 cells could be used to treat ALL-bearing mice using a minor mismatch bone marrow transplant model.…”