Marco Gerlinger

Abstract To explore why PD-L1 scores in metastatic gastro-esophageal adenocarcinomas (GEAs) were significantly lower in a real-world cohort compared with the CheckMate 649 (CM649) trial. PD-L1 combined positive scores (CPS) were evaluated using validated assays in 100 consecutive patients with advanced/metastatic GEA at St Bartholomew’s Hospital (SBH) and compared with CM649 (n = 1567). Clinicopathological factors and biopsy site were analysed to assess their impact on PD-L1 results.

The on-target off-tumour toxicities of T-cell-engaging bispecific antibodies in patients can be captured in intestinal organoids derived from the patients’ biopsied tissue and supplemented with immune cells. Most cancer immunotherapeutics — including bispecific T-cell-engaging antibodies, chimaeric antigen receptor T cells and T cells expressing recombinant T-cell receptors — recognize tumour antigens that are also expressed at lower levels on healthy cells.

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