T-cell reconstitution and expansion after hematopoietic stem cell transplantation: ‘T’ it up!

Abstract

Summary:Adoptive immunotherapy is the isolation and infusion of antigen-specific or nonspecific lymphocytes. Adoptive therapy with T cells may have a role in replacing, repairing, or enhancing immune function damaged by cytotoxic therapies, and rapid lymphocyte recovery may improve outcome after autologous and allogeneic stem cell transplantation (SCT). Recently, a plethora of information on the basic mechanisms of T-cell biology and regulation of cellular immune responses has emerged, permitting the development of new forms of adoptive cell therapy. Efficient ex vivo culture method for T-cell subsets affords the possibility of adoptive transfer of T cells engineered with enhanced capacity for central memory, effector cytotoxicity, Th1, Th2, veto cell, and T regulatory functions. Studies show that homeostatic Tcell proliferation is important for effective adoptive immunotherapy and pretreatment with chemotherapy may enhance the effects of infused T cells. Replicative senescence, in part due to telomere erosion, likely limits successful adoptive immunotherapy, though it may be possible to maintain T-cell pools by enforced expression of telomerase. Clinical trials now demonstrate that it is possible to enhance immune reconstitution after SCT with cytokines or infusions of ex vivo costimulated expanded T cells. These data all support the premise that adoptive therapy can accelerate reconstitution of cellular immunity with enhanced antitumor effects following SCT. Bone Marrow Transplantation (2005) 35, 935-942.

Recombinant IL-7/HGFβ efficiently induces transplantable murine hematopoietic stem cells

“…When combined with the unique signaling properties of rIL-7/HGFβ (see below), the results raise the additional possibility that rIL-7/HGFβ improves the BM microenvironment by increasing the local expression of molecules that regulate self-renewal, expansion, and/or fate determination of HSCs (40). One such defect may be related to the low levels of cytokine production in the irradiated BM, which adversely affect early B-lineage and T-lineage development and the mobilization of HSCs and MPPs (27)(28)(29)(41)(42)(43). Indeed, we have demonstrated here that i.f.…”

Differentiation of naive cord-blood T cells into CD19-specific cytolytic effectors for posttransplantation adoptive immunotherapy

“…2,3 While the feasibility of isolating, expanding, and infusing antigen-specific ␣␤ T-cell receptor (TCR) ϩ T cells from peripheral blood (PB) has been validated in animals and humans, 4-10 the naive function of neonatal T cells precludes a priori identification of resident tumor-specific T cells. Redirecting the specificity of T cells through enforced expression of antigenspecific immunoreceptors and differentiating UCB-derived T cells into cytotoxic T lymphocytes (CTLs) is one approach to overcoming this lack of endogenous tumor-specific T cells specific for desired targets.…”

The characterization and role of leukemia cell-derived dendritic cells in immunotherapy for leukemic diseases

“…Patients with high levels of MRD after chemotherapy are particularly likely to benefit from an early start of a vaccination or with the adoptive transfer of leukemiaspecific T cells enhanced ex vivo (89,107,108). Important evidence suggesting that only mature DCs are suitable for use is because loading immature DCs with antigens will lead to the functional quiescence of T cells resulting from T cell removal or amplification of only regulated T cells (15).…”