Published April 1, 2022
| Version v1
Publication
Open
Hurdles to breakthrough in CAR T cell therapy of solid tumors
Creators
- 1. Tabriz University of Medical Sciences
- 2. Hasanuddin University
- 3. Sechenov University
- 4. Prince Sattam Bin Abdulaziz University
- 5. Iraqi University
- 6. Chiang Mai University
- 7. Chulabhorn Hospital
- 8. Shahid Beheshti University of Medical Sciences
- 9. Tarbiat Modares University
- 10. Stanford University
- 11. Pasteur Institute of Iran
Description
Abstract Autologous T cells genetically engineered to express chimeric antigen receptor (CAR) have shown promising outcomes and emerged as a new curative option for hematological malignancy, especially malignant neoplasm of B cells. Notably, when T cells are transduced with CAR constructs, composed of the antigen recognition domain of monoclonal antibodies, they retain their cytotoxic properties in a major histocompatibility complex (MHC)-independent manner. Despite its beneficial effect, the current CAR T cell therapy approach faces myriad challenges in solid tumors, including immunosuppressive tumor microenvironment (TME), tumor antigen heterogeneity, stromal impediment, and tumor accessibility, as well as tribulations such as on-target/off-tumor toxicity and cytokine release syndrome (CRS). Herein, we highlight the complications that hamper the effectiveness of CAR T cells in solid tumors and the strategies that have been recommended to overcome these hurdles and improve infused T cell performance.
Translated Descriptions
⚠️
This is an automatic machine translation with an accuracy of 90-95%
Translated Description (Arabic)
أظهرت الخلايا التائية الذاتية المهندسة وراثيًا للتعبير عن مستقبلات المستضدات الخيمرية (CAR) نتائج واعدة وظهرت كخيار علاجي جديد للأورام الخبيثة الدموية، وخاصة الأورام الخبيثة للخلايا البائية. والجدير بالذكر أنه عندما يتم نقل الخلايا التائية مع بنيات CAR، المكونة من مجال التعرف على المستضدات للأجسام المضادة وحيدة النسيلة، فإنها تحتفظ بخصائصها السامة للخلايا بطريقة مستقلة عن معقد التوافق النسيجي الرئيسي (MHC). على الرغم من تأثيره المفيد، يواجه نهج العلاج بالخلايا التائية CAR T الحالي تحديات لا تعد ولا تحصى في الأورام الصلبة، بما في ذلك البيئة الدقيقة للورم المثبط للمناعة (TME)، وعدم تجانس مستضدات الورم، والعائق اللحمي، وإمكانية الوصول إلى الورم، بالإضافة إلى المحن مثل السمية المستهدفة/خارج الورم ومتلازمة إطلاق السيتوكين (CRS). هنا، نسلط الضوء على المضاعفات التي تعيق فعالية الخلايا التائية CAR في الأورام الصلبة والاستراتيجيات التي تم التوصية بها للتغلب على هذه العقبات وتحسين أداء الخلايا التائية المنصهرة.Translated Description (French)
Résumé Les lymphocytes T autologues génétiquement modifiés pour exprimer le récepteur antigénique chimérique (CAR) ont montré des résultats prometteurs et sont apparus comme une nouvelle option curative pour la malignité hématologique, en particulier la tumeur maligne des lymphocytes B. Notamment, lorsque les cellules T sont transduites avec des constructions CAR, composées du domaine de reconnaissance des antigènes des anticorps monoclonaux, elles conservent leurs propriétés cytotoxiques de manière indépendante du complexe majeur d'histocompatibilité (CMH). Malgré son effet bénéfique, l'approche actuelle de la thérapie par cellules CAR T est confrontée à une myriade de défis dans les tumeurs solides, notamment le microenvironnement tumoral immunosuppresseur (TME), l'hétérogénéité de l'antigène tumoral, l'empêchement stromal et l'accessibilité tumorale, ainsi que des tribulations telles que la toxicité sur cible/hors tumeur et le syndrome de libération des cytokines (SCR). Ici, nous mettons en évidence les complications qui entravent l'efficacité des cellules CAR T dans les tumeurs solides et les stratégies qui ont été recommandées pour surmonter ces obstacles et améliorer les performances des cellules T infusées.Translated Description (Spanish)
Resumen Las células T autólogas modificadas genéticamente para expresar el receptor de antígeno quimérico (CAR) han mostrado resultados prometedores y han surgido como una nueva opción curativa para la neoplasia maligna hematológica, especialmente la neoplasia maligna de las células B. En particular, cuando las células T se transducen con construcciones CAR, compuestas por el dominio de reconocimiento de antígenos de anticuerpos monoclonales, conservan sus propiedades citotóxicas de una manera independiente del complejo mayor de histocompatibilidad (MHC). A pesar de su efecto beneficioso, el enfoque actual de terapia de células T con CAR enfrenta innumerables desafíos en tumores sólidos, incluido el microentorno tumoral inmunosupresor (TME), la heterogeneidad del antígeno tumoral, el impedimento estromal y la accesibilidad tumoral, así como tribulaciones como la toxicidad en el objetivo/fuera del tumor y el síndrome de liberación de citocinas (CRS). En este documento, destacamos las complicaciones que dificultan la efectividad de las células T CAR en tumores sólidos y las estrategias que se han recomendado para superar estos obstáculos y mejorar el rendimiento de las células T infundidas.Files
s13287-022-02819-x.pdf
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Additional details
Additional titles
- Translated title (Arabic)
- العقبات التي تحول دون تحقيق تقدم في علاج خلايا CAR T للأورام الصلبة
- Translated title (French)
- Obstacles à la percée dans le traitement des tumeurs solides par les cellules CAR T
- Translated title (Spanish)
- Dificultades para avanzar en la terapia de tumores sólidos con células T y CAR
Identifiers
- Other
- https://openalex.org/W4220816662
- DOI
- 10.1186/s13287-022-02819-x
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