Chimeric Antigen Receptor beyond CAR-T Cells

Simple Summary Chimeric antigen receptors (CAR) are engineered molecules expressed on the cell surface that can recognise specific proteins and deliver an activation signal to the cells. Human T lymphocytes equipped with CAR, also called CAR-T cells, can target and kill tumour cells. This technology has been successfully used in treating some of the blood cancers in the last decade. Although the majority of research interest in CAR technology has been focused on CAR-T cells to date, the CAR design has also been used in other types of immune cells to fight against cancers. In this review, we discuss recent advances in CAR design beyond that used in conventional CAR-T cells and their novel indications to develop more potent CAR-based therapy for cancers. Chimeric antigen receptors (CAR) are genetically engineered receptors that can recognise specific antigens and subsequently activate downstream signalling. Human T cells engineered to express a CAR, also known as CAR-T cells, can target a specific tumour antigen on the cell surface to mediate a cytotoxic response against the tumour. CAR-T cell therapy has achieved remarkable success in treating hematologic malignancies, but not in solid tumours. Currently, extensive research is being carried out to make CAR-T cells a therapy for solid tumours. To date, most of the research interest in the field has focused on cytotoxic T lymphocytes as the carrier of CAR products. However, in addition to T cells, the CAR design can be introduced in other immune cells, such as natural killer (NK)/NKT cells, gamma delta T cells, mucosal-associated invariant T (MAIT) cells, dendritic cells (DC), macrophages, regulatory T cells (Treg), B cells, etc. Some of the CAR-engineered immune cells, such as CAR- gamma delta T and CAR-NK/NK-T cells, are directly involved in the anti-tumour response, demonstrated in preclinical studies and/or clinical trials. CAR-Tregs showed promising therapeutic potential in treating autoimmune diseases. In particular, B cells engineered with chimeric receptors can be used as a platform for long-term delivery of therapeutic proteins, such as recombinant antibodies or protein replacement, in an antigen-specific manner. CAR technology is one of the most powerful engineering platforms in immunotherapy, especially for the treatment of cancers. In this review, we will discuss the recent application of the CAR design in non-CAR-T cells and future opportunities in immunotherapy.