CAR T-Cell Therapy for Cancer: Latest Updates and Challenges, with a Focus on B-Lymphoid Malignancies and Selected Solid Tumours

Author:

Tang Hiu Kwan Carolyn1,Wang Bo2,Tan Hui Xian1,Sarwar Muhammad Adeel1,Baraka Bahaaeldin1,Shafiq Tahir1,Rao Ankit R.1

Affiliation:

1. Department of Oncology, Nottingham University Hospitals, Nottingham NG5 1PB, UK

2. University of Cambridge, Trinity Hall, Cambridge CB3 9DP, UK

Abstract

Although exponential progress in treating advanced malignancy has been made in the modern era with immune checkpoint blockade, survival outcomes remain suboptimal. Cellular immunotherapy, such as chimeric antigen receptor T cells, has the potential to improve this. CAR T cells combine the antigen specificity of a monoclonal antibody with the cytotoxic ‘power’ of T-lymphocytes through expression of a transgene encoding the scFv domain, CD3 activation molecule, and co-stimulatory domains. Although, very rarely, fatal cytokine-release syndrome may occur, CAR T-cell therapy gives patients with refractory CD19-positive B-lymphoid malignancies an important further therapeutic option. However, low-level expression of epithelial tumour-associated-antigens on non-malignant cells makes the application of CAR T-cell technology to common solid cancers challenging, as does the potentially limited ability of CAR T cells to traffic outside the blood/lymphoid microenvironment into metastatic lesions. Despite this, in advanced neuroblastoma refractory to standard therapy, 60% long-term overall survival and an objective response in 63% was achieved with anti GD2-specific CAR T cells.

Publisher

MDPI AG

Subject

General Medicine

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