(1080-A) Investigating the in vitro enhancement of differential immune cell responses by immunotherapies pembrolizumab, blinatumomab and trastuzumab

Abstract: Immunotherapies have revolutionised the treatment of several cancers by harnessing the power of the immune system to mediate an durable anti-tumour response. We have investigated three molecules with diverse mechanism of actions in a range of in vitro systems to characterise their impact with the aim of providing discovery platforms for the development of new and enhancing agents.

Pembrolizumab, a checkpoint inhibitor which blocks the PD-1/PDL-1 pathway, enhanced T cell IFNg production, an effect especially pronounced in systems utilising T cells with an ‘exhausted’ phenotype. Blinatumomab, a CD19/CD3 bispecific T cell engager, induced potent killing of a Burkitt lymphoma cell line, and in a PBMC system, at a level that exceeded that of rituximab, an anti-CD20 monoclonal antibody. Finally, we tested the ability of trastuzumab to enhance T cell responses following tumour cell phagocytosis.

These assays highlight the diverse immunological mechanisms that can contribute to the anti-tumour response and are currently being applied to the development of new immunotherapeutic agents.