Discovery of AB680: A Potent and Selective Inhibitor of CD73.

Extracellular adenosine (ADO), present in high concentrations in the tumor microenvironment (TME), suppresses immune function via inhibition of T cell and NK cell activation. Intratumoral generation of ADO depends on the sequential catabolism of ATP by two ecto-nucleotidases, CD39 (ATP → AMP) and CD73 (AMP → ADO). Inhibition of CD73 eliminates a major pathway of ADO production in the TME and can reverse ADO-mediated immune suppression.

Romidepsin Plus Liposomal Doxorubicin Is Safe and Effective in Patients with Relapsed or Refractory T-Cell Lymphoma: Results of a Phase I Dose-Escalation Study.

Purpose: The histone deacetylase (HDAC) inhibitor romidepsin and the anthracycline liposomal doxorubicin (LD) have modest single-agent activity in cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL). We investigated the safety and efficacy of the combination of these two agents in CTCL and PTCL.

Patients And Methods: Using CTCL cell lines and primary CTCL tumor cells, we demonstrated synergistic antitumor activity with romidepsin plus doxorubicin.