Danger Close

May 2, 2024

In artillery and naval gunfire support, the term “danger close” indicates proximity to an intended target that puts friendly forces at risk. It is a warning for them to get out of Dodge ASAP.

However, with the EpicentRx lead oncolytic virus, AdAPT-001, that is armed with a TGF-β trap to neutralize the immunosuppressive protein, TGF-β, danger close sends exactly the opposite message – the need to press forward with the therapeutic attack at full speed.

When AdAPT-001 infects tumor cells, it uses them as a processing factory to replicate in large numbers and to express high levels of the TGF-β trap that it carries. Infection ends with the sudden lysis or rupture of the tumor cells and the release of progeny viral particles, inflammatory chemokines, and cytokines, and so-called “danger signals” that activate immune cells to join the fray and to go on the attack against other tumor cells.

The closer that other therapies like checkpoint inhibitors, which ‘take the brakes off’ T-cells, are to the point of attack, the greater the likelihood that they will contribute to a strong antitumor immune response because of the immune-stimulating properties not only of the virus itself but also the TGF-β trap that AdAPT-001 carries and expresses.

This is a rationale to dose a checkpoint inhibitor and AdAPT-001 not separately but, for all intents and purposes, at the same time in “danger close” range.

So far, in Phase 1 and Phase 2 clinical trials, the administration of AdAPT-001 has led to many casualties on the field of battle. Because these casualties only involve tumor cells, rather than normal cells, which AdAPT-001 is designed not target or harm, the hope – and the observation from clinical trials – is that concomitantly administered checkpoint inhibitors will work better and longer for many more patients, even those that previously were resistant to them.