Engineering CAR-T cells

Zhang, Cheng; Li, Jun; Zhong, Jiang; Zhang, Xi

doi:10.1186/s40364-017-0102-y

Cited by 406 publications

(395 citation statements)

References 57 publications

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“…CARs are synthetic immunoreceptors comprising an extracellular single chain variable fragment (scFv) for the binding of specific surface antigens presented by the target cell [56]. Other extracellular antigen-binding domains are also feasible and comprise e.g.…”

Section: Adoptive Transfer Of Car-transgenic T Cells In the Context Omentioning

confidence: 99%

Specific Adoptive Cellular Immunotherapy in Allogeneic Stem Cell Transplantation

Audehm

Krackhardt²

2017

Oncol Res Treat

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a treatment option for a diversity of advanced hematopoietic malignancies providing hope for long-term responses especially due to immunogenic effects associated with the treatment modality. Despite respectable progress in the field, relapses and/or opportunistic infections are major reasons for the high treatment-related mortality. However, a number of novel immunotherapeutic approaches using defined cell populations have been developed to directly target residual malignant cells as well as defined infectious diseases. We here provide an overview of current adoptive cellular immunotherapies in the context of allo-HSCT and close with an outlook on new directions within the field.

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Section: Adoptive Transfer Of Car-transgenic T Cells In the Context Omentioning

confidence: 99%

Specific Adoptive Cellular Immunotherapy in Allogeneic Stem Cell Transplantation

Audehm

Krackhardt²

2017

Oncol Res Treat

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“…Chimeric antigen receptors are synthetic immune receptors that redirect T cells to eradicate tumors through specific recognition of surface proteins expressed on tumor cells. CARs are fusion proteins comprised of three main components: the extracellular domain responsible for antigen recognition, the intracellular domain responsible for signal transmission, and region that links these two components for flexibility, stability, and dimerization potential composed of the extracellular spacer and transmembrane domain (Figure ) . The intracellular domain contains the T cell co‐receptor CD3ζ, and second‐generation CARs include one co‐stimulatory molecule, such as CD137 (4‐1BB) or CD28, to enhance expansion and persistence .…”

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

167

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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“…Depuis leur développement initial en 1989 les CAR T cells ont évolué en générations successives suivant les caractéristiques de leur domaine intracellulaire ( Figure 1) [4]. Les CAR de 1 re génération contiennent uniquement la sous-unité zeta de la molécule CD3 du complexe TCR/CD mais ne permettent pas de générer un effet anti tumoral satisfaisant [5].…”

Section: éVolution Des Car T Cellsunclassified

CAR-T cells : indications actuelles en pédiatrie et perspectives de développement

et al. 2018

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Les leucémies aiguës lymphoblastiques B (LAL-B) représentent la première cause de cancer chez l'enfant. Malgré un taux de survie à 5 ans supérieur à 90 %, les LAL sont une des causes majeures de décès lié au cancer dans l'enfance. Une nouvelle classe d'immunothérapie se basant sur des lymphocytes T génétiquement modifiés pour exprimer à leur surface un récepteur antigénique chimérique (CAR) ciblant le CD19, marqueur présent sur la majorité des cellules leucémiques B, va potentiellement révolutionner la prise en charge des LAL B en rechute ou réfractaire. Les taux de réponse au traitement vont de 60 % à 90 % dans des essais de phase I/II incluant des patients en deuxième rechute ou plus ou porteurs d'une maladie réfractaire. Des rémissions persistantes voire des guérisons ont été observées. Ces très bons résultats préliminaires permettent d'envisager dans un futur proche leur utilisation en 1 re ligne dans le cas de maladies de particulièrement mauvais pronostic. Cependant la production de ces cellules, leur coût ainsi que la gestion des effets secondaires sont des enjeux majeurs pour le futur de cette thérapeutique. La survenue de rechutes « CD19 négatives » a conduit à élaborer des CARs multispécifiques. Les CAR-T cells allogéniques permettraient quant à elles d'avoir à disposition un arsenal thérapeutique adapté à la cible dès le diagnostic. Les perspectives de développement des CAR T cells résident désormais dans l'optimisation des techniques dans les leucémies et lymphomes et dans l'extension des domaines d'application aux tumeurs solides de l'enfant. Abstract CAR T cells: current indications in children and perspectivesAcute lymphoblastic leukemia (ALL) is the first cause of cancer in children. Five-year overall survival is greater than 90% but leukemia remains a major cause of death from cancer in children.A new class of immunotherapy based on a chimeric antigen receptor "CAR" targeting the CD19 on the B leukemic cells and that is transduced in an autologous or allogenic T lymphocyte will allow to transform the prognosis of refractory or relapsed B-ALL. Overall response rates range

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Engineering CAR-T cells

Cited by 406 publications

References 57 publications

Specific Adoptive Cellular Immunotherapy in Allogeneic Stem Cell Transplantation

Specific Adoptive Cellular Immunotherapy in Allogeneic Stem Cell Transplantation

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

CAR-T cells : indications actuelles en pédiatrie et perspectives de développement

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