Targeting CD73 with a Novel Antibody to Overcome Immunosuppression and Enhance T Cell Responses

High levels of adenosine in the tumor environment suppress the immune system, particularly T cells. CD73, an enzyme that produces adenosine, is found on certain B and T cells and is linked to tumor growth, especially in triple negative breast cancer. Targeting CD73 to reduce adenosine's immunosuppressive effect is a promising therapeutic approach.

Two humanized monoclonal anti-CD73 antibodies were created: CPX-006, which binds directly to the active site of CD73 with high affinity, and CPX-016, which inhibits CD73 allosterically. CPX-006 was shown to completely inhibit CD73 activity in cell assays, unlike CPX-016, which loses effectiveness at high ratios.

CPX-006 was effective in blocking T cell suppression induced by AMP in human PBMCs, with EC50 values indicating its potency in enhancing interferon gamma production and T cell proliferation.

Analysis of CD73 expression in various cancer types revealed heterogeneity in its presence on tumor, immune, and stromal cells. Notably, CD73 was expressed on tumor cells in a significant portion of adenocarcinoma NSCLC cases and to varying degrees in all examined tumor tissues.

The study introduces CPX-006 as a new therapeutic antibody that can fully inhibit CD73's enzymatic activity and restore T cell function. The widespread expression of CD73 in different tumor types suggests it could be a valuable target for immunotherapy.