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.
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 of 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 naïve 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 is registered at www.clinicaltrials.gov as NCT00710892.
- Submitted January 28, 2014.
- Accepted April 14, 2014.
- Copyright © 2014 American Society of Hematology