Engineering and Design of Chimeric Antigen Receptors

Guedan, Sonia; Calderón, Hugo; Posey, Avery D.; Maus, Marcela V.

doi:10.1016/j.omtm.2018.12.009

Cited by 327 publications

(317 citation statements)

References 130 publications

(178 reference statements)

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“…However, persistence differences can also result from qualitative signaling differences driven by the costimulatory domains of the CAR (CD28, 4-1BB, etc.) (18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Single residue in CD28-costimulated CAR-T cells limits long-term persistence and antitumor durability

Guedan

Madar

Casado‐Medrano

et al. 2020

Journal of Clinical Investigation

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129

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“…However, persistence differences can also result from qualitative signaling differences driven by the costimulatory domains of the CAR (CD28, 4-1BB, etc.) (18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Single residue in CD28-costimulated CAR-T cells limits long-term persistence and antitumor durability

Guedan

Madar

Casado‐Medrano

et al. 2020

Journal of Clinical Investigation

Self Cite

129

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“…Optimal CAR design is still an empirical process and highly dependent on antigen‐ and tumor‐specific properties. Innovations in CAR design and its application to the advancement of CAR T cell therapy have been previously reviewed . For brain tumor therapy, we will discuss how CAR design is evolving to address the challenges of tumor antigen escape, the suppressive TME and tumor trafficking.…”

Section: Engineering Tumor Immunity With Carsmentioning

confidence: 99%

CAR T cells for brain tumors: Lessons learned and road ahead

Akhavan

Alizadeh

Wang

et al. 2019

Immunological Reviews

174

161

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Malignant brain tumors, including glioblastoma, represent some of the most difficult to treat of solid tumors. Nevertheless, recent progress in immunotherapy, across a broad range of tumor types, provides hope that immunological approaches will have the potential to improve outcomes for patients with brain tumors. Chimeric antigen receptors (CAR) T cells, a promising immunotherapeutic modality, utilizes the tumor targeting specificity of any antibody or receptor ligand to redirect the cytolytic potency of T cells. The remarkable clinical response rates of CD19‐targeted CAR T cells and early clinical experiences in glioblastoma demonstrating safety and evidence for disease modifying activity support the potential of further advancements ultimately providing clinical benefit for patients. The brain, however, is an immune specialized organ presenting unique and specific challenges to immune‐based therapies. Remaining barriers to be overcome for achieving effective CAR T cell therapy in the central nervous system (CNS) include tumor antigenic heterogeneity, an immune‐suppressive microenvironment, unique properties of the CNS that limit T cell entry, and risks of immune‐based toxicities in this highly sensitive organ. This review will summarize preclinical and clinical data for CAR T cell immunotherapy in glioblastoma and other malignant brain tumors, including present obstacles to advancement.

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“…The order of the variable fragments, as well as the length of the linker, have been shown to affect the antigen binding affinity and stability of the construct. Both the epitope location and abundancy need to be considered when designing the scFv [8].…”

Section: Ectodomainsmentioning

confidence: 99%

“…Amino acid sequences from CD28 or CD8α are commonly used, as well as CH2 and CH3 domains from IgG1, 2, or 4. While both CH2 and CH3 domains can also be utilized to detect CAR expression on the cell's surface, binding between CH2 domains and Fcγ receptors has been observed and can lead to off-target activation [8,11].…”

Section: Ectodomainsmentioning

confidence: 99%

You Have Got a Fast CAR: Chimeric Antigen Receptor NK Cells in Cancer Therapy

Pfefferle

Huntington

2020

Cancers

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The clinical success stories of chimeric antigen receptor (CAR)-T cell therapy against B-cell malignancies have contributed to immunotherapy being at the forefront of cancer therapy today. Their success has fueled interest in improving CAR constructs, identifying additional antigens to target, and clinically evaluating them across a wide range of malignancies. However, along with the exciting potential of CAR-T therapy comes the real possibility of serious side effects. While the FDA has approved commercialized CAR-T cell therapy, challenges associated with manufacturing, costs, and related toxicities have resulted in increased attention being paid to implementing CAR technology in innate cytotoxic natural killer (NK) cells. Here, we review the current landscape of the CAR-NK field, from successful clinical implementation to outstanding challenges which remain to be addressed to deliver the full potential of this therapy to more patients.

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Engineering and Design of Chimeric Antigen Receptors

Abstract: Design and Optimization of CARs CARs are designed in a modular fashion that typically consists of an extracellular target-binding domain, a hinge region, a transmembrane

Cited by 327 publications

References 130 publications

Single residue in CD28-costimulated CAR-T cells limits long-term persistence and antitumor durability

Single residue in CD28-costimulated CAR-T cells limits long-term persistence and antitumor durability

CAR T cells for brain tumors: Lessons learned and road ahead

You Have Got a Fast CAR: Chimeric Antigen Receptor NK Cells in Cancer Therapy

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