Cancer treatment – thinking beyond CAR T-cell therapy

Chimeric antigen receptor (CAR) T-cell therapy is a type of immunotherapy which has gained a lot of attention in recent years. This therapy relies on a chimeric T-cell receptor first introduced in 1987. This discovery led to a development of the first generation CARs by an Israeli immunologist Zelig Eshhar in 1993. Since then, genetically engineered T-cells possessing this chimeric receptor have been used to develop an effective, targeted treatment for various types of cancer. This extensive research resulted in the first FDA-approved CAR T-cell therapy for B-cell lymphomas in 2017. However, this treatment is mostly effective for hematological cancers while solid tumours are particularly difficult to treat. Nevertheless, in recent years there have been many advantages in this field that aimed to modify this therapy for solid tumour treatment. Such methods involve either the combination of CAR T-cell therapy with other cancer immunotherapies, or the use of other types of immune cells, such as natural killer (NK) cells and macrophages. This review article first outlines the principle of CAR T-cell therapy and then discusses new developments in this field, with a particular focus on solid tumours.

Structure and dynamics of the CGRP receptor in apo and peptide-bound forms, and differential modulation of CGRP pathways by migraine therapeutics

G protein-coupled receptors (GPCRs), which mediate the transduction of various extracellular signals to the cell’s interior, belong to one of the largest protein superfamilies in the mammalian genome. As many of these receptors are involved in various physiological processes, they are often targeted in development of therapeutic drugs (Odoemelam et al., 2020). Namely, the calcitonin-gene related peptide receptor has been implicated in migraine pathology and therefore is a target in migraine prophylaxis. Recently, monoclonal antibodies targeting this receptor (anti-CGRP mAbs) have been shown to be effective for this purpose (Bhakta et al., 2021). Nevertheless, more tests examining their efficacy and safety are needed. Firstly, this review article summarises the structure and function of GPCRs, outlining structural characterisation and mode of activation of CGRPRs. Then, it compares the differences in mechanisms of action, efficacy, and safety of different therapeutic drugs for migraine treatment, including anti-CGRP mAbs.