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Combining antibody-drug conjugates with immunotherapy in solid tumors: current landscape and future perspectives

  • Eleonora Nicolò
    Correspondence
    Corresponding author at: Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milan, Italy.
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy

    Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
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  • Federica Giugliano
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy

    Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
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  • Liliana Ascione
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy

    Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
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  • Paolo Tarantino
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy

    Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy

    Breast Oncology Center, Dana-Farber Cancer Institute, Boston, USA

    Harvard Medical School, Boston, USA
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  • Chiara Corti
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy

    Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
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  • Sara M. Tolaney
    Affiliations
    Breast Oncology Center, Dana-Farber Cancer Institute, Boston, USA

    Harvard Medical School, Boston, USA
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  • Massimo Cristofanilli
    Affiliations
    Division of Hematology and Medical Oncology, Weill Cornell Medicine/New York-Presbyterian Hospital, NY, USA
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  • Giuseppe Curigliano
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy

    Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
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Published:April 16, 2022DOI:https://doi.org/10.1016/j.ctrv.2022.102395

      Highlights

      • Antibody-drug conjugates and immunotherapy reshaped the treatment of solid tumors.
      • ADCs exert immunomodulatory activity by interacting with cancer and immune cells.
      • Synergy between ADCs and IO-agents can overcome treatment resistance.
      • Encouraging safety and activity signals have been reported for ADC/IO combinations.
      • Dose optimization and novel immunoconjugates should be the focus of future research.

      Abstract

      Antibody-drug conjugates (ADCs) and immunotherapy have prompted a revolution in the treatment of cancer. However, only a limited fraction of patients obtained a long-term benefit; consequently, combination studies have become a central focus of the current preclinical and clinical research in oncology. A strong biological rationale supports the investigation of combining ADCs with immunotherapy to overcome the occurrence of resistance and improve patient outcomes. ADCs interact with cancer and immune cells by eliciting mechanisms such as immunogenic cell death, antibody-dependent cell-mediated cytotoxicity and dendritic cell activation, ultimately providing potential synergism with immunotherapy. Indeed, ADCs induce tumor-specific adaptive immunity, increasing the infiltration of T cells into the tumor microenvironment, whereas immune-checkpoint inhibitors reinvigorate exhausted T cells, enhancing antitumor immune responses. In light of the promising preclinical data, several clinical trials are currently underway in multiple tumor types to evaluate the safety and activity of combination regimens. Initial evidence from early phase clinical trials has already reported encouraging signals. This review focuses on the combination of ADCs and immunotherapy, highlighting the key mechanisms underlying the synergistic effect and providing an overview of the available clinical evidence in solid tumors. In addition, opportunities to optimize the combination are explored, such as defining the optimal dose, balancing the risks and benefits of dose modifications, and the possibility of developing novel immunoconjugates.

      Keywords

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