TROCEPT: a unique adenovirus for in-tumour expression of immunotherapies via intravenous delivery

TROCEPT is a novel tumor-selective delivery technology based on adenovirus serotype 5 (Ad5). TROCEPT has been engineered to not enter normal human tissues by disabling (de-targeting) all three of the major capsid proteins (fiber knob, hexon and penton). The removal of normal tissue tropisms addresses the main limitations of other intravenously delivered viral therapies, which are rapidly sequestered in the liver and other healthy tissues. TROCEPT has been further engineered to specifically bind to αvβ6 integrin (re-targeting), a tumor marker expressed at high frequency on most carcinomas. The TROCEPT platform can be armed with transgenes encoding protein-based therapeutic drugs for in-tumour expression.

Here, we identified carcinomas with very high frequencies of αvβ6 integrin expression by performing an in-depth IHC analysis using primary tissue from a wide array of carcinomas. We further demonstrate TROCEPTs unique specificity for αvβ6 integrin positive cell entry in vitro and in vivo using mouse xenograft models. Cell entry led to the production of large quantities of functional payload, and viral replication only in tumour cells, demonstrating TROCEPTs potential therapeutic window between tumour and normal tissue. Finally, we performed a series of safety experiments in healthy mice and Syrian golden hamsters and found very little evidence of toxicity (serum cytokines, liver toxicity, weight loss and general health) compared to the parent Ad5 vector.

Taken together, these data support a safe starting dose in humans and form the basis for a preclinical package for TROCEPT-01, which encodes an immune checkpoint inhibitor.