Chimeric Antigen Receptor-T Cells for Targeting Solid Tumors: Current Challenges and Existing Strategies.
BioDrugs
; 33(5): 515-537, 2019 Oct.
Article
en En
| MEDLINE
| ID: mdl-31363930
ABSTRACT
Chimeric antigen receptor-T cells (CAR-Ts) are an exciting new cancer treatment modality exemplified by the recent regulatory approval of two CD19-targeted CAR-T therapies for certain B cell malignancies. However, this success in the hematological setting has yet to translate to a significant level of objective clinical responses in the solid tumor setting. The reason for this lack of translation undoubtedly lies in the substantial challenges raised by solid tumors to all therapies, including CAR-T, that differ from B cell malignancies. For instance, intravenously infused CAR-Ts are likely to make rapid contact with cancerous B cells since both tend to reside in the same vascular compartments within the body. By contrast, solid cancers tend to form discrete tumor masses with an immune-suppressive tumor microenvironment composed of tumor cells and non-tumor stromal cells served by abnormal vasculature that restricts lymphocyte infiltration and suppresses immune function, expansion, and persistence. Moreover, the paucity of uniquely and homogeneously expressed tumor antigens and inherent plasticity of cancer cells provide major challenges to the specificity, potency, and overall effectiveness of CAR-T therapies. This review focuses on the major preclinical and clinical strategies currently being pursued to tackle these challenges in order to drive the success of CAR-T therapy against solid tumors.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Microambiente Tumoral
/
Tratamiento Basado en Trasplante de Células y Tejidos
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Receptores Quiméricos de Antígenos
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Neoplasias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
BioDrugs
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
GENETICA MEDICA
/
TERAPEUTICA
/
TERAPIA POR MEDICAMENTOS
Año:
2019
Tipo del documento:
Article
País de afiliación:
Bélgica