Dose Optimization Trial of Autologous T Cells Engineered to Express Anti-CD19 Chimeric Antigen Receptor (CART-19) in Patients With Relapsed or Refractory CD19+ Chronic Lymphocytic Leukemia (CLL)

This is a randomized, open-label, parallel group study to determine the optimal dose of CART-19 cells (autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR Zeta and 4-1 BB co-stimulatory domains) of the two dose levels being assessed (1-5x10e8 vs. 1-5x10e7 CART-19 cells). This trial will be conducted in two stages.

开始日期2013-01-02

申办/合作机构

University of Pennsylvania

NCT00593944 / Completed临床1期

A Phase 1, Open-Label, Multiple-Dose, Dose-Escalation Study of MDX-1342 in Patients With CD19-Positive Refractory/Relapsed Chronic Lymphocytic Leukemia

The purpose of this study is to see at what dose MDX-1342, a monoclonal antibody, is safe and tolerable for patients with chronic lymphocytic leukemia (CLL). Information on any responses that patients may have to the drug will also be collected.

开始日期2008-08-01

申办/合作机构

Bristol Myers Squibb Co.

100 项与 CD19阳性B细胞慢性淋巴细胞白血病相关的临床结果

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100 项与 CD19阳性B细胞慢性淋巴细胞白血病相关的转化医学

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0 项与 CD19阳性B细胞慢性淋巴细胞白血病相关的专利（医药）

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项与 CD19阳性B细胞慢性淋巴细胞白血病相关的文献（医药）

2021-11-01·JCO Precision Oncology

Rapid and Deep Remission Induced by Blinatumomab for CD19-Positive Chronic Myeloid Leukemia in Lymphoid Blast Phase

作者: Hutchinson, Lloyd ; Higgins, Anne W. ; Bledsoe, Jacob R. ; Gerber, Jonathan M. ; Patel, Shyam A.

2020-02-01·Gene Therapy3区 · 医学

Transposon-mediated generation of CAR-T cells shows efficient anti B-cell leukemia response after ex vivo expansion

3区 · 医学

Article

作者: Bonecker, Simone ; Batista-Silva, Leonardo Ribeiro ; Abdo, Luiza ; Marques, Luisa Vieira Codeço ; Viegas, Mariana ; de Sousa, Priscila ; Alves-Monteiro, Viviane ; Chicaybam, Leonardo ; Monte-Mór, Bárbara ; Bonamino, Martín Hernán

CAR-T-cell therapy has shown considerable advance in recent years, being approved by regulatory agencies in US, Europe, and Japan for the treatment of refractory patients with CD19+ B-cell leukemia or diffuse large B-cell lymphoma. Current methods for CAR-T-cell production use viral vectors for T-cell genetic modification and can take up to 15 days to generate the infusion product. The development of simple and less costly manufacturing protocols is needed in order to meet the increasing demand for this therapy. In this present work, we generated 19BBz CAR-T cells in 8 days using a protocol based on the non-viral transposon-based vector Sleeping Beauty. The expanded cells display mostly a central memory phenotype, expressing higher levels of inhibitory receptors when compared with mock cells. In addition, CAR-T cells were cytotoxic against CD19+ leukemia cells in vitro and improved overall survival rates of mice xenografted with human RS4;11 or Nalm-6 B-cell leukemias. Infused CAR-T cells persisted for up to 28 days, showing that they are capable of long-term persistence and antitumor response. Altogether, these results demonstrate the effectiveness of our protocol and pave the way for a broader application of CAR-T-cell therapy.

2018-10-01·Cancer Cell1区 · 医学

Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting

1区 · 医学

Article

作者: David S. Pitcher ; Xiaolin Xiao ; Katerina Goudevenou ; Mohammed Suhail Chaudhry ; Kyriaki Petevi ; Antonia Rotolo ; Olivier Dubois ; John Maher ; Kikkeri Naresh ; Carolina Kachramanoglou ; Valentina S. Caputo ; Monika Holubova ; Anastasios Karadimitris ; Sandra Iles ; Nicoleta Baxan

Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical remissions in CD19⁺ B cell lymphomas are often short lived. We tested whether CAR19-engineering of the CD1d-restricted invariant natural killer T (iNKT) cells would result in enhanced anti-lymphoma activity. CAR19-iNKT cells co-operatively activated by CD1d- and CAR19-CD19-dependent interactions are more effective than CAR19-T cells against CD1d-expressing lymphomas in vitro and in vivo. The swifter in vivo anti-lymphoma activity of CAR19-iNKT cells and their enhanced ability to eradicate brain lymphomas underpinned an improved tumor-free and overall survival. CD1D transcriptional de-repression by all-trans retinoic acid results in further enhanced cytotoxicity of CAR19-iNKT cells against CD19⁺ chronic lymphocytic leukemia cells. Thus, iNKT cells are a highly efficient platform for CAR-based immunotherapy of lymphomas and possibly other CD1d-expressing cancers.