Bryostatin-1 activity, through the PKC enzyme system, results cellular and intracellular signaling with, among other functions, regulation of cell growth and death. The result is epigenetic modification, the up-regulation of proteins that activate latent cells, and induction of protein and antigen expression on the cell membrane. Host immune effectors as well as immunomodulatory therapeutics are engaged, and their activities enhanced.
The PKC enzyme system can be both activated, and down-regulated by bryostatin-1. Higher doses, and more rapid infusion appears to facilitate down-regulation, while lower doses with longer infusion is expected to heighten activation. The initial clinical trials at the NCI were focused on PKC down-regulation, and the induction of apoptosis. To maximize cellular activation, lower doses are planned for studies in both oncology and HIV.
Bryostatin-1 has been demonstrated both in vitro and in vivo animal models to reverse HIV latency, with activity surpassing other PKC activators (prostratin and ingenol), and the histone deacetylase inhibitors (HDACi). In cancer, bryostatin-1 upregulates tumor antigen expression, a central determinant of efficacy for immunotherapeutics such as chimeric antigen receptor T-cells (CAR-T) and immune checkpoint inhibitors. Thus as a platform approach, BryoLogyx plans early clinical studies of bryostatin-1 in these clinical applications.