Prospects to improve chimeric antigen receptor T-cell therapy for solid tumors

Author:

Jin Chuan1,Yu Di1,Essand Magnus1

Affiliation:

1. Department of Immunology, Genetics & Pathology, Science for Life Laboratory, Uppsala University, SE-75185 Uppsala, Sweden

Abstract

Adoptive transfer of patient-derived T-cells engineered with a chimeric antigen receptor (CAR) targeting the pan-B-cell marker CD19 has led to complete remission in patients with B-cell leukemias while response rates are more modest for B-cell lymphomas. This can be attributed to the fact that the semi-solid structure of lymphomas impedes T-cell infiltration and that the immune suppressive microenvironment within these tumors dampens the effect of CAR T-cells. These obstacles are even more pronounced for solid tumors where dense and often highly immunosuppressive structures are found. This article focuses on different aspects of how to improve CAR T-cells for solid tumors, primarily by decreasing their sensitivity to the harsh tumor microenvironment, by altering the immunosuppressive microenvironment inside tumors and by inducing bystander immunity.

Publisher

Future Medicine Ltd

Subject

Oncology,Immunology,Immunology and Allergy

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