biostudies-literatureWierda WGNCRR NIH HHSFDA HHSNCI NIH HHS1893-900https://www.ebi.ac.uk/biostudies/studies/S-EPMC4556366biostudies-literatureUnknown24(11)Ligation of CD40 on chronic lymphocytic leukemia (CLL) cells induces phenotypic and biochemical changes that facilitate CLL cell-T cell interactions and enhances the sensitivity of CLL cells to clearance by adaptive and innate immune-effector mechanisms. CLL cells can be transduced to express CD40 ligand (CD154) using a replication-defective adenovirus vector, thereby cross-linking CD40 on transduced and non-transduced, bystander CLL cells. In a previous study, patients received infusions of autologous CLL cells, transduced to express murine CD154 (mCD154), which induced anti-leukemic immune responses, but also anti-mCD154 antibodies. In this study, we report a phase I study, in which patients were infused with 1 × 10(8), 3 × 10(8) or 1 × 10(9) autologous CLL cells transduced ex vivo to exLeukemiaA phase I study of immune gene therapy for patients with CLL using a membrane-stable, humanized CD154.PMC4556366M01 RR000827P01 CA081534K08 CA106605R01 FD003427Jalayer AKipps TJMcMannis JWierda WGCastro JEAguillon RSampath DPrussak CEKeating MfalseA phase I study of immune gene therapy for patients with CLL using a membrane-stable, humanized CD154.Ligation of CD40 on chronic lymphocytic leukemia (CLL) cells induces phenotypic and biochemical changes that facilitate CLL cell-T cell interactions and enhances the sensitivity of CLL cells to clearance by adaptive and innate immune-effector mechanisms. CLL cells can be transduced to express CD40 ligand (CD154) using a replication-defective adenovirus vector, thereby cross-linking CD40 on transduced and non-transduced, bystander CLL cells. In a previous study, patients received infusions of autologous CLL cells, transduced to express murine CD154 (mCD154), which induced anti-leukemic immune responses, but also anti-mCD154 antibodies. In this study, we report a phase I study, in which patients were infused with 1 × 10(8), 3 × 10(8) or 1 × 10(9) autologous CLL cells transduced ex vivo to ex2010-01-01T00:00:00Z2010 Nov2025-04-19T14:58:32.9Z2019-03-27T01:57:37ZS-EPMC45563662088205010.1038/leu.2010.191