Efficacy and safety of tisagenlecleucel in adult Japanese patients with relapsed or refractory follicular lymphoma: results from the phase 2 ELARA trial

Fukuhara, Noriko; Katô, Kôji; Goto, Hideki; Tajima, Tsuyoshi; Kawaguchi, Mayu; Tokushige, Kota; Akashi, Koichi; Teshima, Takanori; Harigae, Hideo; Schuster, Stephen J.; Thiéblemont, Catherine; Dreyling, Martin; Fowler, Nathan

doi:10.1007/s12185-022-03481-y

Cited by 3 publications

(3 citation statements)

References 20 publications

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“…Antigen loss is associated with disease relapse and treatment failure in patients undergoing CAR‐T cell therapy as it enables the antigen‐loss variants to escape CAR‐T cell‐mediated immune surveillance. A relapse rate of 10%–57% has been observed in patients with ALL on CAR‐T cell therapy 16,23,24 . Patients who experience antigen loss are also more likely to have limited treatment options.…”

Section: Clinical Implications Of Antigen Lossmentioning

confidence: 99%

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Antigen loss following CAR‐T cell therapy: Mechanisms, implications, and potential solutions

Mishra,

Maiti,

Mohan

et al. 2023

European J of Haematology

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Chimeric Antigen Receptor T‐cell (CAR‐T cell) therapy has emerged as a groundbreaking immunotherapeutic approach for treating various hematological malignancies. CAR‐T cells are engineered to express synthetic receptors that target specific antigens on cancer cells, leading to their eradication. While the therapy has shown remarkable efficacy, a significant challenge that has been observed in 30%–70% of patients showing recurrent disease is antigen loss or downregulation. We searched PubMed/MEDLINE, EMBASE, and Google scholar for articles on antigen loss/escape following Chimeric antigen receptor T‐cell therapy in malignancies. Antigen loss refers to the loss or reduction in the expression of the target antigen on cancer cells, rendering CAR‐T cells ineffective. This phenomenon poses a significant clinical concern, as it can lead to disease relapse and limited treatment options. This review explores the mechanisms underlying antigen loss following CAR‐T cell therapy, its implications on treatment outcomes, and potential strategies to overcome the problem.

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Section: Clinical Implications Of Antigen Lossmentioning

confidence: 99%

“…A relapse rate of 10%-57% has been observed in patients with ALL on CAR-T cell therapy. 16,23,24 Patients who experience antigen loss are also more likely to have limited treatment options.…”

Section: Treatment Failurementioning

confidence: 99%

Antigen loss following CAR‐T cell therapy: Mechanisms, implications, and potential solutions

Mishra,

Maiti,

Mohan

et al. 2023

European J of Haematology

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“…Only one patient with high-risk baseline lymphoma had lymphoma relapse 289 days after tisa-cel infusion. In general, tisa-cel therapy had a manageable safety profile [32].…”

Section: Car-t Cells Anti-cd19mentioning

confidence: 99%

CAR-T Cell Therapy in the Treatment of Pediatric Non-Hodgkin Lymphoma

Ostojska,

Nowak,

Twardowska

et al. 2023

JPM

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Non-Hodgkin lymphomas (NHL) are a group of cancers that originate in the lymphatic system, especially from progenitor or mature B-cells, T-cells, or natural killer (NK) cells. NHL is the most common hematological malignancy worldwide and also the fourth most frequent type of cancer among pediatric patients. This cancer can occur in children of any age, but it is quite rare under the age of 5 years. In recent decades, available medicines and therapies have significantly improved the prognosis of patients with this cancer. However, some cases of NHL are treatment resistant. For this reason, immunotherapy, as a more targeted and personalized treatment strategy, is becoming increasingly important in the treatment of NHL in pediatric patients. The objective of the following review is to gather the latest available research results, conducted among pediatric and/or adult patients with NHL, regarding one immunotherapy method, i.e., chimeric antigen receptor (CAR) T cell therapy. We focus on assessing the effectiveness of CAR-T cell therapy, which mainly targets B cell markers, CD19, CD20, and CD22, their connections with one another, sequential treatment, or connections with co-stimulatory molecules. In addition, we also evaluate the safety, aftermath (especially neurotoxicities) and limitations of CAR-T cell therapy.

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A structural, genetic and clinical comparison of CAR-T cells and CAR-NK cells: companions or competitors?

Andrea,

Chiron,

Sarrabayrouse

et al. 2024

Front. Immunol.

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In recent years, following the groundbreaking achievements of chimeric antigen receptor (CAR) T cell therapy in hematological cancers, and advancements in cell engineering technologies, the exploration of other immune cells has garnered significant attention. CAR-Therapy extended beyond T cells to include CAR natural killer (NK) cells and CAR-macrophages, which are firmly established in the clinical trial landscape. Less conventional immune cells are also making their way into the scene, such as CAR mucosal-associated invariant T (MAIT) cells. This progress is advancing precision medicine and facilitating the development of ready-to-use biological treatments. However, in view of the unique features of natural killer cells, adoptive NK cell immunotherapy has emerged as a universal, allogenic, “off-the shelf” therapeutic strategy. CAR-NK cytotoxic cells present targeted tumor specificity but seem to be devoid of the side effects associated with CAR-T cells. CAR-NK cells appear to be potentially promising candidates for cancer immunotherapy. However, their application is hindered by significant challenges, particularly the limited persistence of CAR-NK cells in the body, which poses a hurdle to their sustained effectiveness in treating cancer. Based upon the foregoing, this review discusses the current status and applications of both CAR-T cells and CAR-NK cells in hematological cancers, and provides a comparative analysis of the structure, genetics, and clinical outcomes between these two types of genetically modified immune cells.

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Efficacy and safety of tisagenlecleucel in adult Japanese patients with relapsed or refractory follicular lymphoma: results from the phase 2 ELARA trial

Cited by 3 publications

References 20 publications

Antigen loss following CAR‐T cell therapy: Mechanisms, implications, and potential solutions

Antigen loss following CAR‐T cell therapy: Mechanisms, implications, and potential solutions

CAR-T Cell Therapy in the Treatment of Pediatric Non-Hodgkin Lymphoma

A structural, genetic and clinical comparison of CAR-T cells and CAR-NK cells: companions or competitors?

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