Details

Autor(en) / Beteiligte

• Zhou, Xiaoou
• Di Stasi, Antonio
• Tey, Siok-Keen
• Krance, Robert A.
• Martinez, Caridad
• Leung, Kathryn S.
• Durett, April G.
• Wu, Meng-Fen
• Liu, Hao
• Leen, Ann M.
• Savoldo, Barbara
• Lin, Yu-Feng
• Grilley, Bambi J.
• Gee, Adrian P.
• Spencer, David M.
• Rooney, Cliona M.
• Heslop, Helen E.
• Brenner, Malcolm K.
• Dotti, Gianpietro

Titel

Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene

Ist Teil von

• Blood, 2014-06, Vol.123 (25), p.3895-3905

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• Adoptive transfer of donor-derived T lymphocytes expressing a safety switch may promote immune reconstitution in patients undergoing haploidentical hematopoietic stem cell transplant (haplo-HSCT) without the risk for uncontrolled graft versus host disease (GvHD). Thus, patients who develop GvHD after infusion of allodepleted donor-derived T cells expressing an inducible human caspase 9 (iC9) had their disease effectively controlled by a single administration of a small-molecule drug (AP1903) that dimerizes and activates the iC9 transgene. We now report the long-term follow-up of 10 patients infused with such safety switch-modified T cells. We find long-term persistence of iC9-modified (iC9-T) T cells in vivo in the absence of emerging oligoclonality and a robust immunologic benefit, mediated initially by the infused cells themselves and subsequently by an apparently accelerated reconstitution of endogenous naive T lymphocytes. As a consequence, these patients have immediate and sustained protection from major pathogens, including cytomegalovirus, adenovirus, BK virus, and Epstein-Barr virus in the absence of acute or chronic GvHD, supporting the beneficial effects of this approach to immune reconstitution after haplo-HSCT. This study was registered at www.clinicaltrials.gov as #NCT00710892. •Allodepleted-T-cells containing the iC9 safety gene persist long-term in vivo, promote immune recovery, and protect against infections.•GvHD caused by iC9-T cells can be permanently controlled by a single administration of AP1903 without abrogating immune reconstitution.