Targeting CD38 Enzymatic Function in Antibody-Driven Immunotherapy for Multiple Myeloma: Insights from Basic Research - Takeaways - MDSpire

Targeting CD38 Enzymatic Function in Antibody-Driven Immunotherapy for Multiple Myeloma: Insights from Basic Research

  • By

  • Alberto L. Horenstein

  • Kristine A. Frerichs

  • Angelo C. Faini

  • Niels W. C. J. van de Donk

  • Fabio Malavasi

  • April 29, 2026

  • 0 min

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  • 1

    CD38 is a multifunctional ectoenzyme that contributes to the immunosuppressive microenvironment in multiple myeloma by degrading NAD+.

  • 2

    Monoclonal antibodies targeting CD38, such as daratumumab and isatuximab, show antitumor activity but face challenges with resistance.

  • 3

    In vitro studies revealed that both daratumumab and isatuximab promote NAD+ degradation and increase ADPR accumulation in multiple myeloma cells.

  • 4

    In vivo, adenosine concentrations in bone marrow plasma remain high during daratumumab therapy, indicating persistent immunosuppression.

  • 5

    Combining CD38-targeted therapies with agents that disrupt adenosinergic signaling may enhance antitumor immunity and improve outcomes in multiple myeloma.

Original Source(s)

Targeting CD38 Enzymatic Function in Antibody-Driven Immunotherapy for Multiple Myeloma: Insights from Basic Research

  • by Alberto L. Horenstein, Kristine A. Frerichs, Angelo C. Faini, Niels W. C. J. van de Donk, Fabio Malavasi

  • April 29, 2026

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