TROCEPT- an oncolytic virus platform engineered for αvβ6 integrin targeted tumour-localized expression of an immune checkpoint inhibitor following intravenous delivery.

TROCEPT is a novel tumour-selective replicating, oncolytic adenovirus type 5 (Ad5) rationally engineered to remove all natural tissue tropisms. This engineering addresses the main limitation of other viral therapies which infect normal tissues and are rapidly removed by the liver and are therefore limited to local delivery. TROCEPT has been further engineered to specifically bind to αvβ6 integrin which is expressed at high frequency in the majority of epithelial cancers, so that following intravenous delivery the virus targets tumour tissue where it replicates and amplifies. In addition, the TROCEPT platform encodes transgenes which enables in-tumour production of powerful therapeutic drugs. The lead programme, TROCEPT-01, encodes a fully human, full length immune checkpoint inhibitor (ICI) antibody. TROCEPT-01 is currently undergoing IND-enabling studies and is expected to enter First in Human studies in 2024 in multiple solid tumour indications. Here we demonstrate viral replication, transgene expression and oncolytic cell death following infection with TROCEPT-01 is highly selective for αvβ6 integrin positive tumour cells compared to a panel of normal human primary cells. Additionally, we show, intravenous delivery in SKOV3 ovarian human tumour xenograft mouse models results in virus delivery, replication, and transgene expression in the tumour. In conclusion, when compared to the parental Ad5 virus, the engineering of TROCEPT-01 leads to more viral delivery to the tumour, less delivery to normal tissue, reduced markers of liver toxicity and reduced inflammatory cytokine release, all of which validate the tumour selectivity and safety profile of the virus.