Combining different anti-cancer immunotherapies is currently a major focus of clinical oncology studies, but while this can increase efficacy this benefit usually comes at a price of increased, dose limiting toxicity. Because these agents are dosed systemically, they frequently cause unwanted immune inflammation in a variety of organ systems as well as in the intended tumor lesions.

Tumor re-engineering aims to overcome these issues by enabling selective delivery to and/or production of the therapeutic agent or combinations in tumor tissues where they are needed while minimizing systemic exposure. We are developing a tumor-specific immune-gene (T-SIGn) vector approach that delivers biotherapeutic gene payloads for production by the tumor cells themselves. These aim to promote anti-tumor immunity from within the lesions by targeting elements of the tumor and local lymphoid microenvironments. This presentation will use data generated with different clinical and preclinical stage T-SIGn candidates to illustrate these concepts.