Outcome of donor-derived TAA-T cell therapy in patients with high-risk or relapsed acute leukemia post allogeneic BMT.
Outcome of donor-derived TAA-T cell therapy in patients with high-risk or relapsed acute leukemia post allogeneic BMT.
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DOI：
10.1182/bloodadvances.2021006831
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发表时间：
2022-04-26
期刊：
影响因子：
7.5
通讯作者：
Bollard, Catherine M.
中科院分区：
文献类型：
--
作者：
Kinoshita, Hannah;Cooke, Kenneth R.;Grant, Melanie;Stanojevic, Maja;Cruz, C. Russell;Keller, Michael;Fortiz, Maria Fernanda;Hoq, Fahmida;Lang, Haili;Barrett, A. John;Liang, Hua;Tanna, Jay;Zhang, Nan;Shibli, Abeer;Datar, Anushree;Fulton, Kenneth;Kukadiya, Divyesh;Zhang, Anqing;Williams, Kirsten M.;Dave, Hema;Dome, Jeffrey S.;Jacobsohn, David;Hanley, Patrick J.;Jones, Richard J.;Bollard, Catherine M.
靶向生存素、PRAME和WT 1的供体来源的肿瘤相关抗原特异性T细胞在BMT后的急性白血病患者中是安全的BMT后早期复发患者的1年OS为42.8%，而88.9%的可评估高危患者在1年时存活。异基因血液或骨髓移植（BMT）后复发的恶性血液病患者对常规挽救治疗的反应有限，预期1年总生存率（OS）<20%。我们评估了一种靶向3种肿瘤相关抗原（TAA-T）的新型T细胞治疗剂在异基因BMT后复发或复发风险高的急性白血病患者中的安全性和临床结局。从BMT供体获得的淋巴细胞被制造为靶向TAA WT 1、PRAME和生存素，这些在大多数血液恶性肿瘤中过度表达和具有免疫原性。患者接受TAA-T输注，剂量为0.5 - 4 × 107/m2。23例复发/难治性（n = 11）和/或高危（n = 12）急性髓性白血病（n = 20）和急性淋巴细胞白血病（n = 3）的骨髓移植受者在移植后输注。无患者发生麻黄碱释放综合征或神经毒性，仅1例患者发生3级移植物抗宿主病。在BMT后复发并接受桥接治疗的患者中，大多数（n = 9/11）在接受TAA-T之前达到完全血液学缓解。TAA-T后复发患者的1年OS为36%，1年无白血病生存率为27.3%。预后最差的患者（移植后复发<6个月）复发后1年OS为42.8%（n = 7）。移植后接受TAA-T的高危患者未达到中位生存期（n = 12）。虽然作为1期研究，允许伴随抗白血病治疗，但TAA-T安全且耐受性良好，在高风险和复发患者中观察到持续缓解。此外，通过T细胞受体V-β测序检测到的过继转移的TAA-T持续至输注后至少1年。本试验在clinicaltrials.gov上注册为#NCT02203903。
Donor-derived, tumor-associated, antigen-specific T cells targeting survivin, PRAME, and WT1 are safe in acute leukemia patients post-BMT. One-year OS in patients who relapsed early post-BMT was 42.8% postrelapse, whereas 88.9% of evaluable high-risk patients were alive at 1 year. Patients with hematologic malignancies relapsing after allogeneic blood or marrow transplantation (BMT) have limited response to conventional salvage therapies, with an expected 1-year overall survival (OS) of <20%. We evaluated the safety and clinical outcomes following administration of a novel T-cell therapeutic targeting 3 tumor-associated antigens (TAA-T) in patients with acute leukemia who relapsed or were at high risk of relapse after allogeneic BMT. Lymphocytes obtained from the BMT donor were manufactured to target TAAs WT1, PRAME, and survivin, which are over-expressed and immunogenic in most hematologic malignancies. Patients received TAA-T infusions at doses of 0.5 to 4 × 107/m2. Twenty-three BMT recipients with relapsed/refractory (n = 11) and/or high-risk (n = 12) acute myeloid leukemia (n = 20) and acute lymphoblastic leukemia (n = 3) were infused posttransplant. No patient developed cytokine-release syndrome or neurotoxicity, and only 1 patient developed grade 3 graft-versus-host disease. Of the patients who relapsed post-BMT and received bridging therapy, the majority (n = 9/11) achieved complete hematologic remission before receiving TAA-T. Relapsed patients exhibited a 1-year OS of 36% and 1-year leukemia-free survival of 27.3% post–TAA-T. The poorest prognosis patients (relapsed <6 months after transplant) exhibited a 1-year OS of 42.8% postrelapse (n = 7). Median survival was not reached for high-risk patients who received preemptive TAA-T posttransplant (n = 12). Although as a phase 1 study, concomitant antileukemic therapy was allowed, TAA-T were safe and well tolerated, and sustained remissions in high-risk and relapsed patients were observed. Moreover, adoptively transferred TAA-T detected by T-cell receptor V-β sequencing persisted up to at least 1 year postinfusion. This trial was registered at clinicaltrials.gov as #NCT02203903.
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DOI：
10.1158/1078-0432.ccr-11-0503
发表时间：
2011-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Klebanoff CA;Gattinoni L;Palmer DC;Muranski P;Ji Y;Hinrichs CS;Borman ZA;Kerkar SP;Scott CD;Finkelstein SE;Rosenberg SA;Restifo NP
通讯作者：
Restifo NP
影响因子：
17.1
作者：
Brentjens RJ;Davila ML;Riviere I;Park J;Wang X;Cowell LG;Bartido S;Stefanski J;Taylor C;Olszewska M;Borquez-Ojeda O;Qu J;Wasielewska T;He Q;Bernal Y;Rijo IV;Hedvat C;Kobos R;Curran K;Steinherz P;Jurcic J;Rosenblat T;Maslak P;Frattini M;Sadelain M
通讯作者：
Sadelain M
影响因子：
20.3
作者：
Lulla, Premal D.;Naik, Swati;Leen, Ann M.
通讯作者：
Leen, Ann M.
影响因子：
20.3
作者：
Rezvani, Katayoun;Yong, Agnes S. M.;Barrett, A. John
通讯作者：
Barrett, A. John
影响因子：
4.3
作者：
Naik, Swati;Martinez, Caridad;Krance, Robert
通讯作者：
Krance, Robert