Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Human gene therapy, 2012-05, Vol.23 (5), p.444-450

Ort / Verlag

United States

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.