Cord blood T cells mediate enhanced antitumor effects compared with adult peripheral blood T cells

Abstract

Key Points• CB T cells mediate enhanced antitumor responses compared with PB T cells in a murine model of B-cell lymphoma.• The antitumor activity correlates with increased tumor-homing of CCR7 high CB CD8 1 T cells and rapid gain of cytotoxic and Th1 function. CD81 T cells and prompt induction of cytotoxic CD8 1 and CD4 1 T-helper (Th1) T cells in the tumor microenvironment. In contrast, in the PB group, this antilymphoma effect is impaired because of delayed tumoral infiltration of PB T cells and a relative bias toward suppressive Th2 and T-regulatory cells. Our data suggest that, despite being naturally programmed toward tolerance, reconstituting T cells after unrelated T-replete CBT may provide superior Tc1-Th1 antitumor effects against high-risk hematologic malignancies. (Blood. 2015;126(26):2882-2891

Clinical separation of cGvHD and GvL and better GvHD-free/relapse-free survival (GRFS) after unrelated cord blood transplantation for AML

“…These findings supported the hypothesis that a more potent GvL effect may be achieved after CBT. Hiwarkar et al 23 recently demonstrated that HLA-mismatch CB T cells mediated superior antitumor responses compared with T cells from donor PB using an experimental model, and this provocative study indicated that CB T cells were intrinsically more effective at GvL. In the present study, more recipients with HLA disparity (85% with 1-or 2-antigen mismatch) and the omission of ATG from the conditioning regimen (T cell replete) could both contribute to the robust GvL effect after CBT.…”

Excellent T-cell reconstitution and survival depend on low ATG exposure after pediatric cord blood transplantation

“…4,5 As timely IR seems essential in preventing RRM and NRM, strategies to improve IR to increase protection against viral disease and relapse of malignancy are warrented. 7,15,27,30 T-cell IR has been associated with the use, dose, and timing of serotherapy, indicating that a higher dose of serotherapy shortly before infusion of the graft is detrimental for timely and robust IR. 6,14,27,31,32 Thus, in vivo exposure of graft-infused T cells to serotherapy results in significant depletion of T cells and limits the exceptional proliferative capacity of cord blood T cells, as recently shown.…”

“…15 Furthermore, the broader T-cell repertoire of reconstituting naive CD4 1 cells after CBT may have an additional advantage over BM and PBSCs, 39 as cord blood cells have an exceptional learning capacity despite their naivety and show a lower incidence of viral reactivation 30 and stronger antileukemic activity. 4,5,7 The high number of naive cells makes CBT a powerful platform for adjuvant cellular therapies (eg, cell vaccinations), 40,41 as the above-mentioned associations suggest that efficient priming of these cells may enhance antileukemic activity.…”

“…2 Furthermore, CBT shows at least comparable survival compared with BM and PBSCs [3][4][5][6] and lower rates of chronic graft-versus-host disease (GVHD), and it has been suggested to have a more potent antileukemic effect compared with traditional stem cell sources. 7,8 When focusing on early T-cell immune reconstitution (IR) (ie, within 3 months after HCT), CBT is suggested to have a slower IR compared with non-T-cell-depleted BM or PBSCs. [9][10][11] Anti-thymocyte globulin (ATG), introduced to the conditioning regimen to prevent GVHD and graft failure, may have a more profound effect on IR after CBT than BM and peripheral blood.…”

The power of cord blood cells

“…5 That cord blood T cells mediate enhanced antitumor effects, compared with adult peripheral blood T cells, was also recently shown in a xenograft Epstein-Barr virus lymphoma model. 6 For the optimal effect, prompt immune reconstitution is essential. The use of ATG in the conditioning is considered to be the major limitation for prompt immune reconstitution after UCBT.…”