Novel approaches to promote CAR T-cell function in solid tumors

TY - JOUR

T1 - Novel approaches to promote CAR T-cell function in solid tumors

AU - Hull, Caroline M.

AU - Maher, John

PY - 2019

Y1 - 2019

N2 - Introduction: Following recent breakthrough developments in the application of CAR T-cell treatments for hematologic cancers, the potential of this approach to achieve meaningful impact against solid tumors now warrants careful consideration. Areas covered: Effective deployment of CAR T-cell immunotherapy for solid tumors has proven challenging to date, due to a series of formidable hurdles. The first of these is the paucity of safe targets for this highly potent, expensive and potentially toxic form of treatment. Compounding this, the tumor microenvironment (TME) constitutes a nexus of cellular and molecular elements that conspire to suppress effective immunological function at that site, corrupting the physiological reparative processes that operate during wound healing. These obstacles are considered with a view to addressing how next-generation CAR T-cell approaches may be effectively applied to different cancer types. Expert opinion: A variety of novel synthetic biology and combinatorial strategies are being developed that can improve CAR T-cell specificity and combat immunosuppressive pathways found in the TME. In addition, recent advances in genome editing techniques are paving the way toward the production of universally applicable CAR T cells.

AB - Introduction: Following recent breakthrough developments in the application of CAR T-cell treatments for hematologic cancers, the potential of this approach to achieve meaningful impact against solid tumors now warrants careful consideration. Areas covered: Effective deployment of CAR T-cell immunotherapy for solid tumors has proven challenging to date, due to a series of formidable hurdles. The first of these is the paucity of safe targets for this highly potent, expensive and potentially toxic form of treatment. Compounding this, the tumor microenvironment (TME) constitutes a nexus of cellular and molecular elements that conspire to suppress effective immunological function at that site, corrupting the physiological reparative processes that operate during wound healing. These obstacles are considered with a view to addressing how next-generation CAR T-cell approaches may be effectively applied to different cancer types. Expert opinion: A variety of novel synthetic biology and combinatorial strategies are being developed that can improve CAR T-cell specificity and combat immunosuppressive pathways found in the TME. In addition, recent advances in genome editing techniques are paving the way toward the production of universally applicable CAR T cells.

KW - cancer

KW - CAR T cell

KW - Chimeric antigen receptor

KW - solid tumor

UR - http://www.scopus.com/inward/record.url?scp=85069484944&partnerID=8YFLogxK

U2 - 10.1080/14712598.2019.1614164

DO - 10.1080/14712598.2019.1614164

M3 - Review article

C2 - 31038366

AN - SCOPUS:85069484944

SN - 1471-2598

VL - 19

SP - 789

EP - 799

JO - EXPERT OPINION ON BIOLOGICAL THERAPY

JF - EXPERT OPINION ON BIOLOGICAL THERAPY

IS - 8

ER -