More About The Marcel van den Brink Lab Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.

CAR T Cells

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies. However graft-versus-host disease (GVHD) and relapse after allo-HSCT remain major causes of morbidity and mortality following transplant. Chimeric antigen receptors (CARs) are non-MHC-restricted T cell receptor-like constructs that confer novel antigen recognition capabilities to T cells, allowing them to proliferate and mediate anti-cancer activity in response to tumor cells. Clinical studies have shown that adoptive transfer of autologous T cells transduced with CARs targeting CD19, which is expressed on normal B cells and several B cell malignancies, is effective against CD19+ malignancies.

To assess the potential of allogeneic CD19-CAR T cells to prevent relapse after allo-HSCT, we are investigating the immunobiology of donor-derived CD19-CAR T cells in preclinical allo-HSCT and lymphoma models. We have generated retroviral vectors encoding mouse CD19-specific CARs, similar to those currently in clinical trials. We have identified that donor CD19-CAR T cells exhibit potent graft-versus-lymphoma (GVL) activity but reduced GVHD activity — a finding that has also been demonstrated in clinical application of allogeneic donor T cells modified with CARs. These findings support the administration of donor CD19-CAR T cells to prevent relapse of CD19+ malignancies after allo-HSCT without increasing the risk for GVHD. Our future directions include delineating the mechanism of reduced GVHD potential of alloreactive T cells bearing CD19-specific CARs and generation of novel receptor constructs that have the potential to inhibit GVHD while retaining GVL.

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