The Taxman

Apr 15, 2024

Tax evasion is much in the news of late. Penalties for it are harsh and may include fines or, imprisonment, or both, as several celebrities can attest to. Safe to assume they share – or at least can relate to – the darkly satirical anti-tax sentiment from the famous song, Taxman, by the Beatles:

“I’ll tax the street
If you try to sit, I’ll tax your seat
If you get too cold, I’ll tax the heat
If you take a walk, I’ll tax your feet
Don’t ask me what I want it for
If you don’t want to pay some more
‘Cause I’m the taxman, yeah, I’m the taxman”

Like these celebrity tax evaders that conceal or attempt to conceal their true income from the IRS (Internal Revenue System), cancer cells are immune evaders that illicitly hide out from the RES (Reticuloendothelial System), the immune tax collectors, composed mainly of monocytes/macrophages. The penalty of discovery is eradication, which strongly motivates the tumor cells to stay well and truly hidden.

One of the main camouflage strategies that tumors avail themselves of is an immunosuppressive cytokine called transforming growth factor-beta (TGF-β). The overexpression of this cytokine tends to render tumors insensitive to treatment with immunotherapies like checkpoint inhibitors.

The EpicentRx lead therapy, AdAPT-001, is an oncolytic adenovirus that expresses a TGF-β trap for the elimination of TGF-β, which, as emerging clinical data suggests, makes formerly camouflaged tumors visible to the immune system. This is especially the case when AdAPT-001 is combined with a checkpoint inhibitor that “takes the brakes off” T cells and further activates antitumor immunity. The result in some cases has been regression of otherwise completely resistant tumors.

Tumors are inveterate tax scofflaws but, fortunately, the Taxman, AdAPT-001, is on the case, and in the ongoing Phase 2 trial called BETA PRIME it has come to collect on the enormous debt owed to the RES and the rest of the immune system.