Feasibility, long-term safety, and immune monitoring of regulatory T cell therapy in living donor kidney transplant recipients.
Feasibility, long-term safety, and immune monitoring of regulatory T cell therapy in living donor kidney transplant recipients.
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DOI：
10.1111/ajt.16395
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Lombardi G
中科院分区：
文献类型：
--
作者：
Harden PN;Game DS;Sawitzki B;Van der Net JB;Hester J;Bushell A;Issa F;Brook MO;Alzhrani A;Schlickeiser S;Scotta C;Petchey W;Streitz M;Blancho G;Tang Q;Markmann J;Lechler RI;Roberts ISD;Friend PJ;Hilton R;Geissler EK;Wood KJ;Lombardi G
肾移植的短期预后会因移植失败和免疫抑制毒性引起的死亡率而受到损害。自体多克隆调节性T细胞（Treg）治疗的免疫调节可能促进免疫抑制的减少，促进更好的长期临床结果。在一项I期临床试验中，12名肾移植受者在移植后第5天接受1-10 × 106 Treg / kg治疗，以代替诱导免疫抑制（Treg治疗队列）。19例患者接受标准免疫抑制（参考队列）。主要结局是无排斥反应和患者生存。患者和移植成活率均为100%；移植后48个月，Treg治疗组的急性无排斥生存率为100%，而参考队列为78.9%。Treg疗法没有显示出过度的安全问题。Treg治疗组中有4例患者成功停用霉酚酸酯，并继续接受他克莫司单药治疗。Treg输注导致外周血Treg的长期剂量依赖性增加，同时边缘区B细胞数量增加。我们发现了一种移植前免疫表型，表明体外Treg扩增失败的风险很高。自体Treg治疗是可行的，安全的，并且与标准免疫抑制相比，可能具有更低的排异率。Treg治疗可能为减少免疫抑制治疗和改善长期预后提供了一个令人兴奋的机会。
Short-term outcomes in kidney transplantation are marred by progressive transplant failure and mortality secondary to immunosuppression toxicity. Immune modulation with autologous polyclonal regulatory T cell (Treg) therapy may facilitate immunosuppression reduction promoting better long-term clinical outcomes. In a Phase I clinical trial, 12 kidney transplant recipients received 1–10 × 106 Treg per kg at Day +5 posttransplantation in lieu of induction immunosuppression (Treg Therapy cohort). Nineteen patients received standard immunosuppression (Reference cohort). Primary outcomes were rejection-free and patient survival. Patient and transplant survival was 100%; acute rejection-free survival was 100% in the Treg Therapy versus 78.9% in the reference cohort at 48 months posttransplant. Treg therapy revealed no excess safety concerns. Four patients in the Treg Therapy cohort had mycophenolate mofetil withdrawn successfully and remain on tacrolimus monotherapy. Treg infusion resulted in a long-lasting dose-dependent increase in peripheral blood Tregs together with an increase in marginal zone B cell numbers. We identified a pretransplantation immune phenotype suggesting a high risk of unsuccessful ex-vivo Treg expansion. Autologous Treg therapy is feasible, safe, and is potentially associated with a lower rejection rate than standard immunosuppression. Treg therapy may provide an exciting opportunity to minimize immunosuppression therapy and improve long-term outcomes.
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影响因子：
15.3
作者：
Schneider, Martin A;Meingassner, Josef G;Lipp, Martin;Moore, Henrietta D;Rot, Antal
通讯作者：
Rot, Antal
影响因子：
8.8
作者：
Sanchez-Fueyo, Alberto;Whitehouse, Gavin;Lombardi, Giovanna
通讯作者：
Lombardi, Giovanna
DOI：
10.1016/j.omtm.2018.01.006
发表时间：
2018-03-16
期刊：
Molecular therapy. Methods & clinical development
影响因子：
--
作者：
Fraser H;Safinia N;Grageda N;Thirkell S;Lowe K;Fry LJ;Scottá C;Hope A;Fisher C;Hilton R;Game D;Harden P;Bushell A;Wood K;Lechler RI;Lombardi G
通讯作者：
Lombardi G
影响因子：
8.8
作者：
Ekberg, H.;Bernasconi, C.;Halloran, P. F.
通讯作者：
Halloran, P. F.
影响因子：
168.9
作者：
Sayegh, Mohamed H.;Remuzzi, Giuseppe
通讯作者：
Remuzzi, Giuseppe