CAR T-cell immunotherapy: The path from the by-road to the freeway?

TY - JOUR

T1 - CAR T-cell immunotherapy

T2 - The path from the by-road to the freeway?

AU - Whilding, Lynsey M.

AU - Maher, John

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Chimeric antigen receptors are genetically encoded artificial fusion molecules that can re-program the specificity of peripheral blood polyclonal T-cells against a selected cell surface target. Unparallelled clinical efficacy has recently been demonstrated using this approach to treat patients with refractory B-cell malignancy. However, the approach is technically challenging and can elicit severe toxicity in patients. Moreover, solid tumours have largely proven refractory to this approach. In this review, we describe the important structural features of CARs and how this may influence function. Emerging clinical experience is summarized in both solid tumours and haematological malignancies. Finally, we consider the particular challenges imposed by solid tumours to the successful development of CAR T-cell immunotherapy, together with a number of innovative strategies that have been developed in an effort to reverse the balance in favour of therapeutic benefit.

AB - Chimeric antigen receptors are genetically encoded artificial fusion molecules that can re-program the specificity of peripheral blood polyclonal T-cells against a selected cell surface target. Unparallelled clinical efficacy has recently been demonstrated using this approach to treat patients with refractory B-cell malignancy. However, the approach is technically challenging and can elicit severe toxicity in patients. Moreover, solid tumours have largely proven refractory to this approach. In this review, we describe the important structural features of CARs and how this may influence function. Emerging clinical experience is summarized in both solid tumours and haematological malignancies. Finally, we consider the particular challenges imposed by solid tumours to the successful development of CAR T-cell immunotherapy, together with a number of innovative strategies that have been developed in an effort to reverse the balance in favour of therapeutic benefit.

KW - Cancer

KW - Chimeric antigen receptor

KW - Immunotherapy

KW - Solid tumours

KW - T-cells

UR - http://www.scopus.com/inward/record.url?scp=84951801466&partnerID=8YFLogxK

U2 - 10.1016/j.molonc.2015.10.012

DO - 10.1016/j.molonc.2015.10.012

M3 - Article

AN - SCOPUS:84951801466

SN - 1574-7891

VL - 9

SP - 1994

EP - 2018

JO - Molecular Oncology

JF - Molecular Oncology

IS - 10

ER -