The one-two punch (of CAR T cells)

Shah, Nirali N.

doi:10.1182/blood.2019004272

Cited by 7 publications

(7 citation statements)

References 10 publications

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“…The authors reported a minimal residual diseasenegative response rate of 96.0% among the 51 ALL patients and a median progression-free survival of 13.6 months (with a median follow-up of 16.7 months) (111). The benefits of a sequential CAR T cell infusion strategy including an increased leukemia-free survival rate were corroborated by other studies (112,113). Fig.…”

Section: Multi-targeting Cars 321 Dual-targeting Strategiesmentioning

confidence: 62%

In Like a Lamb; Out Like a Lion: Marching CAR T Cells Toward Enhanced Efficacy in B-ALL

Kozani

O’Connor

2021

Molecular Cancer Therapeutics

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Combining synthetic biology with adoptive T-cell transfer has led to promising advances in the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), diffuse large B-cell lymphoma (DLBCL), and mantle cell lymphoma (MCL). Chimeric antigen receptors (CARs) are synthetic receptors that redirect T-cell specificity against cancer. CARs include “built-in” signaling domains that reprogram T-cell metabolism, enhance effector function, and support long-term persistence. Despite their success in blood-based malignancies, relapse can occur in CD19-redirected CAR T-cell therapies for several reasons, including poor engraftment, impaired in vivo proliferation, and T-cell senescence. Herein, we explain how subtle alterations in CAR design may overcome barriers to effective adoptive immunotherapy. We also discuss how the physiochemical properties of the single-chain variable fragment (scFv) affect differentiation and persistence. Moreover, we describe innovative advances in CAR engineering and provide insight into the development of humanized scFvs whose proposed benefits include increased persistence and improved clinical outcomes. Tumor cells can evade CAR T-cell–mediated detection and elimination due to the emergence or presence of CD19-negative leukemic cell subpopulations. We also discuss the opportunities and challenges in targeting other B-ALL–associated antigens. Identifying alternate targets is fundamentally necessary to restore the success of CAR T-cell therapies in CD19-negative patients with B-ALL.

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Section: Multi-targeting Cars 321 Dual-targeting Strategiesmentioning

confidence: 62%

In Like a Lamb; Out Like a Lion: Marching CAR T Cells Toward Enhanced Efficacy in B-ALL

Kozani

O’Connor

2021

Molecular Cancer Therapeutics

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“…In this case, the CAR-T cell is intended to recognize a target cell with a certain antigen and interact with it. 189 Considering the limitations of genetic modification, many researchers have tried to use DNA nanostructures to complement the use of genetic engineering in cell-based immunotherapy. 81,[190][191][192] For instance, Liu et al reported an aptamer-based self-assembled DNA nanostructure that is multivalent and bispecific with a view to mediate intercellular interactions (Fig.…”

Section: Programming Cell-cell Adhesionmentioning

confidence: 99%

DNA nanostructures for exploring cell–cell communication

Wang,

Xiong,

Shi

et al. 2024

Chem. Soc. Rev.

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“…Many interventions were investigated for CD19+ re-lapse, such as humanized or full human CAR vectors and immune-checkpoint inhibitors among others 5 . To reduce the relapse rate, combination interventions are investigated in our and many other centers, such as allogeneic stem cell transplantation (allo-HCT), dual-target CAR T cell therapies, and sequential CD19/22 CAR-T infusion 9,[31][32][33][34] . Allo-HCT is one of the combination interventions recommended for patients with EMD infiltration, high-risk cytogenetics, and special mutations associated with poor prognoses after CAR-T cell therapies in our group 9,33 .…”

Section: Combination Interventionsmentioning

confidence: 99%

Chimeric Antigen Receptor T Cell Therapy for Acute Leukemia

2023

BCT

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The worldwide use of CD19 chimeric antigen receptor (CAR)-T cells has increased the response rate in patients with refractory or relapsed B-cell acute lymphoblastic leukemia. Clinical practice has become much safer with the help of immunotherapy-related toxicity management guidelines, such as the ASTCT consensus grading system. Tocilizumab and steroids are the major interventions for controlling cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). New drugs and interventions for uncontrolled CRS and ICANS, including JAK1/2 inhibitors, have also been investigated. The combination of ruxolitinib and steroids effectively controlled severe CRS without impeding CAR-T cell expansion. Patients with refractory CNS3 status and CNS masses were excluded from the clinical trials because of the high risk of severe ICANS. Intracranial injections of steroids and Ommaya capsule implantation were effective. For some heavily treated patients, the difficulties in CAR-T cell manufacturing and expansion may be resolved by combination with blinatumumab. Relapse is a major concern after CAR-T therapy, and combination interventions, such as allogeneic stem cell transplantation, dual-target CAR-T cell therapies, and sequential CD19/22 CAR-T infusion, have been investigated in many centers. For T-lineage-targeted CAR-T therapies, the CAR T-cell fratricide can be overcome using many techniques. The efficacy and safety of CD7+ CAR-T cell therapy have been widely reported in recent years. A high response rate can be achieved when the immune reconstitution is prolonged. Infections, particularly viral reactivations, should be carefully monitored, as relapses are another potential issue. Switching targets and eliminating residual CD7+ CAR-T cells in the blood are key points for patients who relapse after CD7+ CAR-T cell therapy. CAR-T cell therapies for AML have not been investigated in a large-scale cohort, except for CD19-positive AML with the AML1-ETO fusion gene.

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The one-two punch (of CAR T cells)

Cited by 7 publications

References 10 publications

In Like a Lamb; Out Like a Lion: Marching CAR T Cells Toward Enhanced Efficacy in B-ALL

In Like a Lamb; Out Like a Lion: Marching CAR T Cells Toward Enhanced Efficacy in B-ALL

DNA nanostructures for exploring cell–cell communication

Chimeric Antigen Receptor T Cell Therapy for Acute Leukemia

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