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    Myeloma Novel Drug Targets and agents

    Category: Myeloma Novel Drug Targets and agents

    Enhancing Immunotherapy through Metabolic Modulation in Humanized Multiple Myeloma Mice

    (PA-301) Enhancing Immunotherapy through Metabolic Modulation in Humanized Multiple Myeloma Mice

    Wednesday, September 17, 2025
    Introduction: Multiple myeloma (MM) is characterized by the proliferation of monoclonal plasma cells.

    Metabolic disorders with high energy metabolism and glycolysis rates in the bone marrow ensure

    sufficient energy for the rapid proliferation and growth of MM cells. Phosphatase of regenerating

    liver-3 (PRL3) inhibitor, a potent modulator of energy metabolism, emerges as an effective drug

    for MM. However, its limited impact on immune system activation compromises therapeutic

    efficacy.

    Methods: The study involved synthesizing the target compound TCP and preparing TCP@PRL3 NPs. The

    effects of TCP@PRL3 NPs on DC activation, T cell function and cell metabolism were verified by

    flow cytometry, western blot and central carbon metabolism at the cellular and animal levels

    Results: This study proposes a therapeutic approach utilizing PRL3 inhibitor to enhance photodynamic

    therapy (PDT) mediated immunogenic cell death (ICD). Mechanically, the metabolomics study

    results demonstrated that PRL3 inhibition can reduce the produce of L-lactic acid and ameliorate

    the acidic tumor micro environment to enhance the immune cell function. In addition to

    conceptual validation in high-energy metabolism CT26 tumors and lowimmunogenicity 4T1

    tumors, we co-administered daratumumab (a CD38 antibody) and validated this strategy in

    humanized multiple myeloma mice, providing a robust potential solution for the clinical

    treatment of high-energy metabolism and low-immunogenicity tumors.

    Conclusions: The study demonstrated the potential of TCP@PRL3 NPs combined with light irradiation to

    modulate energy metabolism and enhance immune therapy. This approach led to increased

    anti-tumor immune responses by regulating tumor proliferation rates, inducing immunogenic cell

    death (ICD), and reshaping the tumor microenvironment (TME) in humanized multiple myeloma

    mice. However, challenges such as off-target effects and limited penetration depth remain,

    suggesting the need for further optimization and development of advanced strategies for

    effective immunotherapy.