Paving the road to make chimeric antigen receptor-T-cell therapy effective against solid tumors

Abstract

The three major standard therapies, that is, surgery, chemotherapy, and radiation therapy have conventionally been applied to the treatments for cancers and have saved many patients. In addition, for intractable, refractory, or advanced malignancies that cannot be cured by the three standard therapies, immunotherapy is an important subject of basic and clinical researches. Immune checkpoint inhibitor therapy (ICI) has shown significant therapeutic efficacies on some types of tumors in large-scale randomized clinical trials, making a major impact on clinical oncology by scientifically proving and establishing the effectiveness of an immunotherapy. In 2018, ICI was awarded the Nobel Prize in Physiology or Medicine, and immunotherapy is now becoming the "fourth" standard therapy for cancers. Recently, adoptive cell therapies, in which genetically modified T cells with enhanced reactivity against tumors are infused into the patients, have been attracting considerable attention as a hopeful immunotherapy following ICI. Particularly, chimeric antigen receptor (CAR)-T-cell therapies demonstrate marked therapeutic efficacies against some hematologic malignancies, and have been approved in many countries. However, current CAR-T-cell therapy is considered to be little effective against solid tumors, which is one of the challenging issues to be overcome in CAR-T-cell therapy. In this review, we at first introduce CAR and CAR-T cell, and then focus on the recent progress of CAR-T-cell therapy against solid tumors as well as the novel concept on a role of CAR-T cells, aiming to further understandings of the novel cancer immunotherapies.

Keywords: antigen heterogeneity; chimeric antigen receptor; migration; solid tumors; tumor microenvironment.