Immune checkpoint inhibitors (e.g. CTLA-4, PD-L1) have recently shown significant promise in the treatment of cancer. However, when used alone, these checkpoint inhibitors are limited by the absence or repression of immune cells within the targeted cancer. For those cancers associated with these limited immune systems, there remains a need for effective therapies. Agents capable of recruiting and activating immune cells to these types of cancers could extend the overall and complete response rates of combination therapies within the immunooncology domain.
Researchers at the National Cancer Institute (NCI) have developed a combination therapy capable of recruiting and activating immune cells for the treatment of cancer. This therapy incorporates, HMGN1, an alarmin, which recruits immune cells using its chemotactic-induction capabilities, and activates dendritic cell maturation via its TLR4 agonism. The combination of HMGN1 with TLR7/8 agonism and immune-checkpoint inhibition has been tested in xenograft models. In those models, mice bearing ~1cm tumors were successfully treated and resistant to re-challenge. Development of this combination continues and is available for in-licensing and co-development.