Co-expression patterns of chimeric antigen receptor (CAR)-T cell target antigens in primary and recurrent ovarian cancer

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.

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

Acta Pharmaceutica Sinica B ◽

10.1016/j.apsb.2020.12.015 ◽

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

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Invasive Fungal Infections after Anti-CD19 Chimeric Antigen Receptor-Modified T-Cell Therapy: State of the Evidence and Future Directions

Journal of Fungi ◽

10.3390/jof7020156 ◽

2021 ◽

Vol 7 (2) ◽

pp. 156

Author(s):

Will Garner ◽

Palash Samanta ◽

Ghady Haidar

Keyword(s):

Risk Factors ◽

T Cell ◽

Cell Therapy ◽

Chimeric Antigen Receptor ◽

Fungal Infections ◽

Antigen Receptor ◽

Invasive Fungal Infections ◽

T Cell Therapy ◽

Car T Cell ◽

Car T

Studies describing invasive fungal infections (IFIs) after chimeric antigen receptor-modified T-cell (CAR-T-cell) therapy are limited. Although post-CAR-T-cell IFIs appear to be uncommon, they are associated with significant morbidity and mortality. Specific risk factors for IFIs in CAR-T-cell recipients have not been fully characterized and are often extrapolated from variables contributing to IFIs in patients with other hematologic malignancies or those undergoing hematopoietic cell transplant. Optimal prophylaxis strategies, including the use of yeast versus mold-active azoles, also remain ill-defined. Further research should investigate key risk factors for IFIs and establish an evidence-based approach to antifungal prophylaxis in these patients in order to improve clinical outcomes.

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

Transplantation and Cellular Therapy ◽

10.1016/s2666-6367(21)00260-8 ◽

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

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OP206 Expert Elicitation Of Probabilistic Distributions to Inform Survival Modelling of CD19 Chimeric Antigen Receptor T-Cell Therapies

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462320000951 ◽

2020 ◽

Vol 36 (S1) ◽

pp. 3-3

Author(s):

Niamh Carey ◽

Conor Hickey ◽

Laura Mc Cullagh ◽

Michael Barry

Keyword(s):

T Cell ◽

Chimeric Antigen Receptor ◽

Antigen Receptor ◽

Expert Elicitation ◽

Cell Transplant ◽

Major Advance ◽

Cell Therapies ◽

Risk Of Death ◽

Car T Cell ◽

Car T

IntroductionIn 2018, the National Centre for Pharmacoeconomics (NCPE) was commissioned to conduct a health technology assessment (HTA) of one of the first commercially available chimeric antigen receptor (CAR) T-cell therapies, tisagenlecleucel. CAR T-cells are a major advance in personalized cancer treatment, demonstrating promising outcomes in relapsed/refractory pediatric acute lymphoblastic leukemia (pALL). However, the results are based on short-term follow up, limiting their value in predicting long-term survival and leading to uncertainty about the most appropriate survival modeling method to employ. This study aimed to address these limitations by means of expert elicitation.MethodsAn expert elicitation method, the histogram technique, was employed. A predefined discrete numerical scale was presented in Microsoft Excel® and the expert was asked to place twenty crosses on a frequency chart. These crosses represented the expert's beliefs about the distribution of particular quantities. Each cross represented five percent of the probabilistic distribution. Individual distributions were then aggregated across experts using linear pooling.ResultsA total of seventeen experts were invited to take part; eight agreed to participate and five completed the exercise. Three experts did not consider tisagenlecleucel to be a “curative” therapy because patients had a higher risk of death, compared with the age- and sex-matched general population. The aggregated distributions indicated the five-year overall survival rate to be thirty-three percent (95% CI 8.65–56.88) in patients who do not receive a subsequent stem cell transplant and twenty percent (95% CI 2.38 -52.04) in those who do.ConclusionsThe results of this study will be used to calibrate CD19 CAR T-cell therapy survival estimates presented in HTA submissions to the NCPE to ensure more robust assessments. They will also be used to inform the construction of a de novo cost-utility model for examining the cost effectiveness of CD19 CAR T-cell therapies for relapsed/refractory pALL in the Irish healthcare setting.

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Hypogammaglobulinemia after Chimeric Antigen Receptor (CAR) T-cell therapy: characteristics, management, and future directions

The Journal of Allergy and Clinical Immunology In Practice ◽

10.1016/j.jaip.2021.10.037 ◽

2021 ◽

Author(s):

Jeanette Wat ◽

Sara Barmettler

Keyword(s):

T Cell ◽

Cell Therapy ◽

Chimeric Antigen Receptor ◽

Antigen Receptor ◽

Future Directions ◽

T Cell Therapy ◽

Car T Cell ◽

Car T Cell Therapy ◽

Car T

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

Neuro-Oncology ◽

10.1093/neuonc/noab196.582 ◽

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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