Cemiplimab

T cells mediate antitumour activity following activation by antigen receptor signalling and CD28 costimulatory signalling. T cell proliferation and activation are regulated by a number of T cell immune regulatory checkpoints, including programmed death-1 (PD-1). PD-1 is an inhibitory co-receptor that is predominantly expressed on the surface of T cells to block T cell activation. Its ligands, PD-L1 and PD-L2, bind to PD-1 to activate downstream signalling cascades that ultimately result in the inhibition of T cell function such as T cell proliferation, cytokine production, and cytotoxicity. PD-1 receptor signalling pathway serves to maintain tolerance and regulate any ineffective or harmful immune responses; however, PD-1 signalling can also attenuate immune responses in cases where such protection is needed, such as autoimmune disorders and malignancy.

PD-L1 and PD-L2 are expressed on antigen-presenting cells (APCs) as well as on some types of tumour cells as part of an adaptive immune response by tumours. PD-1 is also upregulated in some cancers, impeding T cell-mediated antitumour activity. Cemiplimab is a human PD-1-blocking antibody that binds to PD-1 and blocks its interaction with its ligands. By disinhibiting PD-1 mediated suppression of T cell activity, cemiplimab works to potentiate T cell cytotoxicity against tumours.