Infusion of CD19-directed/multivirus specific-cytotoxic T lymphocytes after allogeneic hematopoietic stem cell transplantation for B cell malignancies

      Allogeneic hematopoietic stem cell transplant (HSCT) may increase long term disease-free survival in patients with high-risk-B-cell malignancies, but is associated with delayed immune reconstitution contributing to viral infections and relapse. We hypothesized that a single T-cell platform mediating both antiviral and antileukemic activity may be beneficial. We prepared CTLs with specificities directed towards EBV/CMV/adenovirus, then engineered them to express chimeric antigen receptors (CAR) targeting CD19 (expressed by B-cell malignancies). Donor-derived antigen presenting cells were transduced with an Ad5f35 vector encoding CMVpp65 transgene to stimulate and expand multivirus specific T cells. After 3 stimulations, multivirus-specific T cells were transduced with a retroviral vector encoding CAR-CD19.28 zeta.
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