Pre-clinical development of Chimeric Antigen Receptor T-cell immunotherapy: implications of design for efficacy and safety

TY - JOUR

T1 - Pre-clinical development of Chimeric Antigen Receptor T-cell immunotherapy: implications of design for efficacy and safety

AU - Halim, Leena

AU - Ajina, Adam

AU - Maher, John

PY - 2018/4/21

Y1 - 2018/4/21

N2 - Following the landmark approvals by the United States Food and Drug Administration, the adoptive transfer of CD19-directed chimeric antigen receptor (CAR) T-cells has now entered mainstream clinical practice for patients with chemotherapy-resistant or refractory B-cell malignancies. These approvals have followed on from a prolonged period of pre-clinical evaluation, informing the design of clinical trials that have demonstrated unprecedented efficacy in this difficult to treat patient population. However, the delivery of autologous CAR-engineered T-cell therapy is complex, costly and not without significant risk. Here we summarize the key themes of CAR T-cell preclinical development and highlight a number of innovative strategies designed to further address toxicity and improve efficacy. In concert with the emerging promise of precision genome editing, it is hoped these next generation products will increase the repertoire of clinical applications of CAR T-cell therapy in malignant and perhaps other disease settings.

AB - Following the landmark approvals by the United States Food and Drug Administration, the adoptive transfer of CD19-directed chimeric antigen receptor (CAR) T-cells has now entered mainstream clinical practice for patients with chemotherapy-resistant or refractory B-cell malignancies. These approvals have followed on from a prolonged period of pre-clinical evaluation, informing the design of clinical trials that have demonstrated unprecedented efficacy in this difficult to treat patient population. However, the delivery of autologous CAR-engineered T-cell therapy is complex, costly and not without significant risk. Here we summarize the key themes of CAR T-cell preclinical development and highlight a number of innovative strategies designed to further address toxicity and improve efficacy. In concert with the emerging promise of precision genome editing, it is hoped these next generation products will increase the repertoire of clinical applications of CAR T-cell therapy in malignant and perhaps other disease settings.

KW - Adoptive cell therapy

KW - chimeric antigen receptor

KW - engineering

KW - cancer immunotherapy

U2 - 10.1016/j.beha.2018.04.002

DO - 10.1016/j.beha.2018.04.002

M3 - Article

SN - 1521-6926

JO - Baillieres Best Practice & Research in Clinical Haematology

JF - Baillieres Best Practice & Research in Clinical Haematology

ER -