Role of CAR-T cell therapy in B-cell acute lymphoblastic leukemia

Greinix, Hildegard

doi:10.1007/s12254-019-00541-8

Cited by 5 publications

(4 citation statements)

References 32 publications

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“…In addition, gene editing, which involves the modification, deletion, or addition of DNA, is another tool in the application of gene therapy to pediatric malignancies ( Zhang et al, 2021b ). Of note in this category is CAR T-cell therapy, which showed efficacy when tested in pediatric leukemia ( Greinix, 2019 ). Promising results have also been observed in preliminary studies when PD-1 was edited to induce T cells to attack osteosarcoma tumors ( Fan et al, 2021 ).…”

Section: Clinical Applications and Success Stories In Pediatric Cancermentioning

confidence: 99%

Advances and challenges in gene therapy strategies for pediatric cancer: a comprehensive update

Moaveni,

Amiri,

Shademan

et al. 2024

Front. Mol. Biosci.

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Pediatric cancers represent a tragic but also promising area for gene therapy. Although conventional treatments have improved survival rates, there is still a need for targeted and less toxic interventions. This article critically analyzes recent advances in gene therapy for pediatric malignancies and discusses the challenges that remain. We explore the innovative vectors and delivery systems that have emerged, such as adeno-associated viruses and non-viral platforms, which show promise in addressing the unique pathophysiology of pediatric tumors. Specifically, we examine the field of chimeric antigen receptor (CAR) T-cell therapies and their adaptation for solid tumors, which historically have been more challenging to treat than hematologic malignancies. We also discuss the genetic and epigenetic complexities inherent to pediatric cancers, such as tumor heterogeneity and the dynamic tumor microenvironment, which pose significant hurdles for gene therapy. Ethical considerations specific to pediatric populations, including consent and long-term follow-up, are also analyzed. Additionally, we scrutinize the translation of research from preclinical models that often fail to mimic pediatric cancer biology to the regulatory landscapes that can either support or hinder innovation. In summary, this article provides an up-to-date overview of gene therapy in pediatric oncology, highlighting both the rapid scientific progress and the substantial obstacles that need to be addressed. Through this lens, we propose a roadmap for future research that prioritizes the safety, efficacy, and complex ethical considerations involved in treating pediatric patients. Our ultimate goal is to move from incremental advancements to transformative therapies.

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Section: Clinical Applications and Success Stories In Pediatric Cancermentioning

confidence: 99%

Advances and challenges in gene therapy strategies for pediatric cancer: a comprehensive update

Moaveni,

Amiri,

Shademan

et al. 2024

Front. Mol. Biosci.

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“…Multiple alternative B-cell associated antigens are found to persist in CD19-negative relapse in B-cell malignancies, posing therapeutic opportunities that investigators hope to exploit in ongoing clinical trials. Additional antigenic targets under investigation include CD37 (4-passage transmembrane protein), CD10 (common acute lymphocytic leukemia antigen), TSLPR (thymic stromal lymphopoietin receptor), CD70 (protein expressed on highly-active B- and T-lymphocytes), and CD30 (TNF receptor-related surface protein expressed on activated B- and T-lymphocytes) [ 55 , 56 , 57 , 58 , 59 ]. Scarfo et al [ 56 ] recently published their preclinical development of anti-CD37 single targeted CAR and anti-CD19/anti-CD37 dual targeted CAR T cells for B-cell malignancies.…”

Section: B-cell Malignanciesmentioning

confidence: 99%

Bispecific Chimeric Antigen Receptor T Cell Therapy for B Cell Malignancies and Multiple Myeloma

Cronk

Zurko

Shah

2020

Cancers

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Chimeric antigen receptor (CAR) modified T cell therapy offers a targeted immunotherapeutic approach to patients with refractory hematological malignancies. This technology is most advanced in B cell malignancies and multiple myeloma and is rapidly evolving as more data become available regarding clinical efficacy and response durability. Despite excellent initial response rates with single antigen targeting CARs, failure to respond to therapy and relapse due to target antigen downregulation remain clinical challenges. To mitigate immunophenotypic selective pressures, simultaneous dual antigen targeting with bispecific CAR T cells or multiple administration of different populations of CAR T cells may prevent relapse by addressing one resistance mechanism attributed to antigenic loss. This article will review recently published data on the use of dual targeting with CAR T cells from early phase clinical trials aimed at treating B cell malignancies and multiple myeloma.

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“…Various antigens have been explored as potential targets for T-cell therapies in hematological and solid tumors. For instance, CD19 is used for B-cell acute lymphoblastic leukemia (B-ALL) 2 and chronic lymphocytic leukemia (CLL). The majority of patients with relapsed or refractory B-ALL (R/R B-ALL) and CD19-targeted CAR-T cells have achieved complete disease remission 3 .…”

Section: Introductionmentioning

confidence: 99%

CAR-T-Cell Therapy: Present Progress and Future strategies

Abbasi

Riaz

Khawar³

et al. 2022

Biomed. Res. Ther.

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Chimeric antigen receptor (CAR) T-cell therapy is a type of immunotherapy that uses the patient's immune system. It creates cancer-killing T cells through genetic modification that targets tumor antigens. CAR consists of three fundamental units, the extracellular, transmembrane, and intracellular domains. CARs are rapidly evolving with progress in the field of immunotherapy starting from first-generation CARs to next-generation CARs. Different cancer types, including B-cell malignancies, are being treated by CAR-T therapy. The FDA has approved two CAR-T therapies, namely, tisagenlecleucel and axicabtagene ciloleucel. The recently approved CAR-T products are Lisocabtagene maraleucel and Idecabtagene vicleucel. Despite the success of CAR-T therapy, several limitations, including cytokine release syndrome and neurotoxicity, need to be overcome. In the present review, we have provided an overview of CAR generations, their applications, potential limitations, and possible solutions for improving CAR-T therapy for a variety of tumor types.

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Role of CAR-T cell therapy in B-cell acute lymphoblastic leukemia

Cited by 5 publications

References 32 publications

Advances and challenges in gene therapy strategies for pediatric cancer: a comprehensive update

Advances and challenges in gene therapy strategies for pediatric cancer: a comprehensive update

Bispecific Chimeric Antigen Receptor T Cell Therapy for B Cell Malignancies and Multiple Myeloma

CAR-T-Cell Therapy: Present Progress and Future strategies

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