Trial of Adoptive Immunotherapy With TRACT to Prevent Rejection in Living Donor Kidney Transplant Recipients
Status:
Completed
Trial end date:
2016-06-16
Target enrollment:
Participant gender:
Summary
Regulatory CD4+CD25+ T cells (Treg) derived from the thymus and/or peripheral tissues have
been demonstrated to broadly control T cell reactivity (14). Importantly, Tregs have been
shown to control immune responsiveness to alloantigens and significantly contribute to
operational tolerance in transplantation models (15, 16). However, there have been limited
efforts to harness the therapeutic potential of directly isolated CD4+CD25+ Treg cells for
controlling graft rejection and inducing transplantation tolerance, such as for kidney
transplants. In order for CD4+CD25+ Treg cells to be used as a clinical treatment, the
following cell properties could be necessary: ex vivo generation of sufficient numbers of
cells, migration in vivo to sites of antigenic reactivity, ability to suppress rejection in
an alloantigen-specific manner, and survival/expansion after infusion for a critical, but
currently unknown, period of time. Our published work and that of other investigators has
demonstrated 1) the feasibility of expanding Treg ex vivo, 2) the ability of these cells to
downregulate allogeneic immune responses in vitro, and 3) the efficacy of Treg for prevention
of allograft rejection in animal models (15,16). We have developed strategies for the ex vivo
expansion of naturally occurring human Tregs (nTregs) that allow for the practical employment
of this cellular therapy in the clinic. Our central hypothesis is that sufficient human nTreg
can be expanded ex vivo and used to both prevent renal transplant rejection and facilitate
the reduction and subsequent withdrawal of drug-based immunosuppression. This study will
allow for us to define the safety of Treg adoptive cellular transfer (TRACT) in living donor
renal transplant recipients that draws upon our extensive preclinical experience with
expanded Tregs, as well as our recognized clinical expertise with designing immunosuppressive
regimens compatible with this type of therapeutic cell transfer.