Toxicities of CD19 CAR‐T cell immunotherapy

Hirayama, Alexandre V.; Turtle, Cameron J.

doi:10.1002/ajh.25445

Cited by 120 publications

(106 citation statements)

References 57 publications

(160 reference statements)

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“…Cytokine release syndrome onset typically occurs during the first week after CART cell treatment. However, patients treated with 4-1BB-costimulated CART cells often experience later onset of CRS than patients treated with CD28-costimulated CART cells ( 25 ). CRS onset usually coincides near the peak of CART cell expansion and cytokine production.…”

Section: Cytokine Release Syndromementioning

confidence: 99%

Neurotoxicity and Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy: Insights Into Mechanisms and Novel Therapies

2020

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Chimeric antigen receptor T (CART) cell immunotherapy has been remarkably successful in treating certain relapsed/refractory hematological cancers. However, CART cell therapy is also associated with toxicities which present an obstacle to its wider adoption as a mainstay for cancer treatment. The primary toxicities following CART cell administration are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). New insights into the mechanisms of these toxicities have spurred novel treatment options. In this review, we summarize the available literature on the clinical manifestations, mechanisms, and treatments of CART-associated CRS and ICANS.

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Section: Cytokine Release Syndromementioning

confidence: 99%

Neurotoxicity and Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy: Insights Into Mechanisms and Novel Therapies

2020

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“…Cytokine release syndrome and neurological complications are commonly reported with CD19 CAR T therapy. 12 Caused by the release of inflammatory cytokines by both the infused CAR-T cell and bystander immune cells, CRS is a systemic illness that closely mimics sepsis. Patients typically develop a fever, which may be followed by haemodynamic instability, capillary leak and multiorgan failure in severe cases.…”

Section: Administration and Toxicity Managementmentioning

confidence: 99%

Delivery of adoptive cell therapy in the context of the health-care system in the UK: challenges for clinical sites

Pillai

Davies

Thistlethwaite

2020

Therapeutic Advances in Vaccines and Immunotherapy

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Advanced Therapy Medicinal Products (ATMPs) comprise novel cell, tissue and gene therapies and offer the potential of durable remissions for diseases where there is a high unmet clinical need. Once considered a niche area of academic research, ATMPs now represent one of the fastest-growing areas of clinical development. The field has seen a rapid expansion of academic and commercial entities successfully translating ATMP research into the clinic. This is reflected in projection that the global gene and cell therapy market will be worth US $11.96 billion by 2025. However, these treatments are complex to deliver and frequently do not fit naturally into established healthcare systems. In the United Kingdom (UK) there has been a long-standing interest in ATMP research and, in order to meet the ambition to act as an international hub of activity for delivery of ATMPs, a collaborative network of Advanced Therapy Treatment Centres (ATTCs) has been established. This review explores the challenges of delivery in the clinical setting, focussing on one form of ATMP, Adoptive Cell Therapy (ACT). We describe the strategy being implemented in the UK to optimise the roll-out of these exciting new therapies.

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“…Early translation of CAR-T cells in human must focus on safety and e cacy [23]. Some clinical studies about CAR-T cell therapy have indicated that severe and occasionally fatal toxicities can occur [24][25][26]. CRS is a major toxicity [27].…”

Section: Car-t Distribution and The Safety In Nhl Patientsmentioning

confidence: 99%

Distribution Measurements of Chimeric Antigen Receptor-Modified T Cells Against CD19

Ying¹,

He²,

Wang³

et al. 2020

Preprint

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Backgroud: The unprecedented efficacy of chimeric antigen receptor (CAR) T-cell immunotherapy of CD19+ B-cell malignancies has opened a new and useful way for the treatment of malignant tumor. Nonetheless, there are still formidable challenges in the field of CAR-T cell therapy, such as the biodistribution of CAR-T cells in vivo.Methods: We demonstrated the distribution of CAR-T cells in the absence of target cells or with target cells in the mice and the dynamic changes in the patient blood over time after infusion were deteced by qPCR and FACS. Results: CAR-T cells still proliferated in the mice without target cells and peaked at 2 weeks. However, CAR-T cells did not increase significantly in the presence of target cells within 2 weeks after infusion, but expanded at 6 weeks. In the clinical trial, we found that CAR-T cells peaked at 7-21days after infusion and can last for as long as 510 days in the peripheral blood of patients. Simultaneously, mild side-effects were noted which can be effectively controlled within two months in these patients.Conclusions: CAR-T cells can expand themselves with or without target cells in mice. CAR-T cells can persistence for a long time in patients.

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Toxicities of CD19 CAR‐T cell immunotherapy

Cited by 120 publications

References 57 publications

Neurotoxicity and Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy: Insights Into Mechanisms and Novel Therapies

Neurotoxicity and Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy: Insights Into Mechanisms and Novel Therapies

Delivery of adoptive cell therapy in the context of the health-care system in the UK: challenges for clinical sites

Distribution Measurements of Chimeric Antigen Receptor-Modified T Cells Against CD19

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