CD7 CAR T Cells for the Therapy of Acute Myeloid Leukemia

Gomes-Silva, Diogo; Atilla, Erden; Atilla, Pinar Ataca; Mo, Feiyan; Tashiro, Haruko; Srinivasan, Madhuwanti; Lulla, Premal; Rouce, Rayne H.; Cabral, Joaquim M. S.; Ramos, Carlos A.; Brenner, Malcolm K.; Mamonkin, Maksim

doi:10.1016/j.ymthe.2018.10.001

Cited by 101 publications

(80 citation statements)

References 46 publications

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“…Latest multi-center BCMA-CAR trials results indicate a relatively safe profile (although cytokine release syndrome -CRS and transient neurotoxicity were observed) with an overall response rate over 90% [145,146]. Other antigens currently being targeted to treat hematological malignancies include CD20 for NHL, CD138 for MM [144], CD33 [147], CD123 for AML [148,149] and CD7 for certain leukemias and lymphomas [150]. Lately, using a very elegant approach to treat T-cell malignancies, Pule and colleagues isolated an antibody specific for the TCRβ1 constant region.…”

Section: Beyond Cd19: New Car-t Cells For Solid Tumors -In Search Ofmentioning

confidence: 99%

T-cells “à la CAR-T(e)” – Genetically engineering T-cell response against cancer

Eisenberg

Hoogi

Shamul

et al. 2019

Advanced Drug Delivery Reviews

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Section: Beyond Cd19: New Car-t Cells For Solid Tumors -In Search Ofmentioning

confidence: 99%

T-cells “à la CAR-T(e)” – Genetically engineering T-cell response against cancer

Eisenberg

Hoogi

Shamul

et al. 2019

Advanced Drug Delivery Reviews

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“…It is also expressed in approximately 30% of patients with AML and has been correlated with low expression of wild type CEBPA and a worse prognosis [47][48][49][50][51][52][53], making it an attractive immunotherapeutic target. However, because it is also expressed on most mature T cells, additional engineering and processing techniques are necessary to avoid fratricide when using T cell-based therapies to target CD7 [54].…”

Section: Antigens Present In Distinct Aml Subsetsmentioning

confidence: 99%

Harnessing T Cells to Target Pediatric Acute Myeloid Leukemia: CARs, BiTEs, and Beyond

Epperly

Velasquez

2020

Children

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Outcomes for pediatric patients with acute myeloid leukemia (AML) remain poor, highlighting the need for improved targeted therapies. Building on the success of CD19-directed immune therapy for acute lymphocytic leukemia (ALL), efforts are ongoing to develop similar strategies for AML. Identifying target antigens for AML is challenging because of the high expression overlap in hematopoietic cells and normal tissues. Despite this, CD123 and CD33 antigen targeted therapies, among others, have emerged as promising candidates. In this review we focus on AML-specific T cell engaging bispecific antibodies and chimeric antigen receptor (CAR) T cells. We review antigens being explored for T cell-based immunotherapy in AML, describe the landscape of clinical trials upcoming for bispecific antibodies and CAR T cells, and highlight strategies to overcome additional challenges facing translation of T cell-based immunotherapy for AML.

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“…Unlike B‐cell lymphomas, T‐cell lymphomas are associated with an overall poor prognosis and have limited therapeutic options . Targeting T‐cell malignancies with CAR‐T cells is more challenging due to shared antigen expression between normal, malignant, and therapeutic CAR‐T cells, potentially leading to CAR‐T cell fratricide (self‐killing) and prolonged T‐cell aplasia . Unlike the manageable B‐cell aplasia caused by CD19 CAR‐T cells, T‐cell targeted CAR‐Ts may cause profound immunodeficiency similar to that seen following allogeneic stem cell transplant (SCT) leading to increased risk of severe infections.…”

Section: Car‐t Cells For the Treatment Of T‐cell Lymphomasmentioning

confidence: 99%

CAR‐T cell therapy for non‐Hodgkin lymphomas: A new treatment paradigm

2019

Self Cite

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Non-Hodgkin lymphomas (NHLs), the most common hematologic malignancy, are comprised of a heterogeneous group of lymphoid malignancies derived from both B-cell and T-cell progenitors or mature T cells, and rarely natural killer (NK) cells. Among the heterogeneous NHL subtypes, diffuse large B-cell lymphoma (DLBCL) is by far the most common aggressive lymphoma, accounting for 30%-35% of all NHLs diagnosed. The majority of patients can be cured with combination chemoimmunotherapy upfront or with salvage high dose chemotherapy and autologous hematopoietic stem cell transplantation (ASCT). 1 However, 15%-20% of patients will relapse or develop chemo-refractory disease 1-4 and these patients have a dismal prognosis, particularly if they are chemo-resistant to salvage therapy or relapse following ASCT. 5-8 A recent retrospective meta-analysis of patients who achieved stable disease or progressive disease as the best response to chemotherapy, or who relapsed within 12 months of autologous transplant, showed an overall response rate (ORR) of only 26% to salvage therapy and median overall survival (OS) of 6.3 months. 8 The outcomes for other aggressive NHL subtypes are equally poor after the failure of combination chemotherapy. This study further highlights the unmet need for novel Abstract The majority of patients with B-cell non-Hodgkin lymphoma (NHL) can be cured with standard chemoimmunotherapy. However, patients who fail first line therapy have dismal outcomes, particularly if they have disease that is resistant to salvage therapy, including chemoimmunotherapy, radiation and/or autologous stem cell transplantation. Indolent B-NHLs, such as follicular lymphoma (FL), although not generally considered curable may be treated over many years with good prognosis. However, a subset of indolent B-NHLs can undergo histologic transformation into more aggressive subtypes with outcomes similar to aggressive B-NHLs. In recent years, T cells, genetically modified with chimeric antigen receptors, have demonstrated a remarkable capacity to induce complete and durable clinical responses in patients with chemotherapy-refractory lymphomas. Indeed, two autologous CD19-directed CARmodified T-cell products have now been FDA-approved for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma and transformed FL, while a plethora of other CAR-T cell targets are being explored in ongoing clinical trials. The purpose of this review is to summarize the clinical efficacy and unique toxicities of individually developed CAR-T cell products for the treatment of lymphomas, and their evolution from the laboratory bench to commercialization. K E Y W O R D S cancer, CAR-T cell, chimeric antigen receptor, immunotherapy, lymphoma, oncology

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CD7 CAR T Cells for the Therapy of Acute Myeloid Leukemia

Cited by 101 publications

References 46 publications

T-cells “à la CAR-T(e)” – Genetically engineering T-cell response against cancer

T-cells “à la CAR-T(e)” – Genetically engineering T-cell response against cancer

Harnessing T Cells to Target Pediatric Acute Myeloid Leukemia: CARs, BiTEs, and Beyond

CAR‐T cell therapy for non‐Hodgkin lymphomas: A new treatment paradigm

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