scholarly journals Cytokine release syndrome and neurotoxicity after CD19 chimeric antigen receptor-modified (CAR-) T cell therapy

2018 ◽  
Vol 183 (3) ◽  
pp. 364-374 ◽  
Author(s):  
Kevin A. Hay
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Management of cytokine release syndrome and neurotoxicity in chimeric antigen receptor (CAR) T cell therapy

2019 ◽  
Vol 12 (3) ◽  
pp. 195-205 ◽  
Author(s):  
Utkarsh H. Acharya ◽  
Tejaswini Dhawale ◽  
Seongseok Yun ◽  
Caron A. Jacobson ◽  
Julio C. Chavez ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

scholarly journals Etanercept as a new therapeutic option for cytokine release syndrome following chimeric antigen receptor T cell therapy

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Lina Zhang ◽  
Shuai Wang ◽  
Ji Xu ◽  
Run Zhang ◽  
Han Zhu ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Tnf Α ◽  
Car T

AbstractCytokine release syndrome (CRS) is the most common toxicity induced by chimeric antigen receptor (CAR) T cell therapy. At present, anti-IL-6 agents including tocilizumab and siltuximab have been applied in the treatment of CRS. However, tocilizumab and siltuximab are expensive and some patients fail to respond to anti-IL-6 therapy, which urges the need for new drugs. In clinical practice, we found some patients with multiple myeloma developed markedly increased levels of tumor necrosis factor (TNF)- α during the CRS period after anti-BCMA CAR T cell infusion. Here we present the successful use of TNF-α inhibitor (etanercept) to cure CRS in three patients. The introduction of etanercept did not alter patients' response to CAR T cell therapy and no adverse event was observed directly related to the administration of etanercept. Furthermore, in vitro experiments confirmed that etanercept did not affect the proliferation and effector function of CAR T cells. Our results indicate that etanercept could be considered as a treatment option for CRS in patients with significantly elevated TNF-α levels.

Chimeric antigen receptor T cells immunotherapy: challenges and opportunities in hematological malignancies

Immunotherapy ◽  
2020 ◽  
Vol 12 (18) ◽  
pp. 1341-1357
Author(s):  
Nashwa El-Khazragy ◽  
Sherief Ghozy ◽  
Passant Emad ◽  
Mariam Mourad ◽  
Diaaeldeen Razza ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Hematological Malignancies ◽  
Antigen Receptor ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Challenges And Opportunities

Taking advantage of the cellular immune system is the mainstay of the adoptive cell therapy, to induce recognition and destruction of cancer cells. The impressive demonstration of this principle is chimeric antigen receptor-modified T (CAR-T)-cell therapy, which had a major impact on treating relapsed and refractory hematological malignancies. Despite the great results of the CAR-T-cell therapy, many tumors are still able to avoid immune detection and further elimination, as well as the possible associated adverse events. Herein, we highlighted the recent advances in CAR-T-cell therapy, discussing their applications beneficial functions and side effects in hematological malignancies, illustrating the underlying challenges and opportunities. Furthermore, we provide an overview to overcome different obstacles using potential manufacture and treatment strategies.

scholarly journals Cancer stem cell-targeted chimeric antigen receptor (CAR)-T cell therapy: Challenges and prospects

2020 ◽  
Author(s):  
Javad Masoumi ◽  
Abdollah Jafarzadeh ◽  
Jalal Abdolalizadeh ◽  
Haroon Khan ◽  
Jeandet Philippe ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Cell Therapy ◽  
Cancer Stem Cell ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

scholarly journals Continuous Telemetry Monitoring in Chimeric Antigen Receptor (CAR) T-Cell Therapy Patients

2021 ◽  
Vol 27 (3) ◽  
pp. S211-S212
Author(s):  
Eddie Stephens ◽  
Ansh Mehta ◽  
Tanya Persoon ◽  
Shannon Baker ◽  
Remy David ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

NCMP-10. DYSGRAPHIA AS THE EARLIEST PRESENTING SYMPTOM OF SEVERE CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY NEUROTOXICITY: A SINGLE CENTER EXPERIENCE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi149-vi149
Author(s):  
Carlen Yuen ◽  
Kourosh Rezania ◽  
Thomas Kelly ◽  
Michael Bishop
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
B Cell Lymphoma ◽  
Motor Dysfunction ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Abstract INTRODUCTION Chimeric antigen receptor (CAR) T-cell therapy, including axicabtagene ciloleucel (axi-cel; Yescarta®) and tisagenlecleucel (tisa-cel; Kymriah®), are FDA approved for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Neurotoxicity (NT) associated with CAR T-cell therapy (immune effector cell-associated neurotoxicity syndrome [ICANS]) can be fatal. Timely data, in the form of an abbreviated bedside mini-mental status exam, is thought to lead to earlier identification of NT. However, existing literature validating this method is limited. MATERIALS AND METHODS In this retrospective study, patients with R/R DLBCL treated with commercial axi-cel or tisa-cel in our center from December 2017 to September 2018 were assessed for NT with the CTCAE v4 criteria and the CAR-T-cell-therapy-associated TOXicity (CARTOX-10) scoring system. RESULTS Twenty-six patients with R/R DLBCL were treated with CAR T-cell therapy (25 axi-cel/[Yescarta®] and 1 tisagenlecleucel [Kymriah®]). Twenty-three (88%) developed NT with 8 (31%) experiencing severe NT (Grade III-IV). Tremor and dysgraphia occurred in all patients with severe NT. Lower average CARTOX-10 score (p=< 0.01), dysgraphia (p< 0.01), inattention (p=.018), and disorientation (p=.01) were significantly associated in patients with severe NT. A trend towards significance was observed between tremor and severe NT (p=.08). All patients with severe NT had both dysgraphia and tremor 8/8 (100%) and 2/8 (25%) had concurrent dysnomia. Death occurred in 12/26 (46%) of patients due to disease progression (n=11) and cardiac failure due to myositis (n=1). CONCLUSION In our limited cohort, dysgraphia, inattention, and disorientation are heralding symptoms of severe NT in adult R/R DLBCL patients treated with commercial CAR T-cell therapy. Dysgraphia was the earliest presenting symptom in patients with severe CAR T-cell neurotoxicity and was likely a manifestation of motor dysfunction rather than a component of dysphasia. Further studies with a larger cohort are needed to validate our findings.

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