Infusing CD19-directed T cells to augment disease control in patients undergoing autologous hematopoietic stem-cell transplantation for advanced B-lymphoid malignancies

Partow Kebriaei, Helen Huls, Bipulendu Jena, Mark Munsell, Rineka Jackson, Dean A. Lee, Perry B. Hackett, Gabriela Rondon, Elizabeth Shpall, Richard E. Champlin, Laurence J.N. Cooper

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

Limited curative treatment options exist for patients with advanced B-lymphoid malignancies, and new therapeutic approaches are needed to augment the efficacy of hematopoietic stem-cell transplantation (HSCT). Cellular therapies, such as adoptive transfer of T cells that are being evaluated to target malignant disease, use mechanisms independent of chemo-and radiotherapy with nonoverlapping toxicities. Gene therapy is employed to generate tumor-specific T cells, as specificity can be redirected through enforced expression of a chimeric antigen receptor (CAR) to achieve antigen recognition based on the specificity of a monoclonal antibody. By combining cell and gene therapies, we have opened a new Phase I protocol at the MD Anderson Cancer Center (Houston, TX) to examine the safety and feasibility of administering autologous genetically modified T cells expressing a CD19-specific CAR (capable of signaling through chimeric CD28 and CD3-ζ) into patients with high-risk B-lymphoid malignancies undergoing autologous HSCT. The T cells are genetically modified by nonviral gene transfer of the Sleeping Beauty system and CAR + T cells selectively propagated in a CAR-dependent manner on designer artificial antigen-presenting cells. The results of this study will lay the foundation for future protocols including CAR+ T-cell infusions derived from allogeneic sources.

Original languageEnglish (US)
Pages (from-to)444-450
Number of pages7
JournalHuman gene therapy
Volume23
Issue number5
DOIs
StatePublished - May 1 2012

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