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Bystander effect of antibody–drug conjugates: fact or fiction?

  • Breast Cancer (RA Leon Ferre, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Purpose of review

Summarizing the current preclinical and clinical evidence about bystander effect of antibody–drug conjugates (ADCs) in solid tumors.

Recent findings

One of the main challenges of treating solid tumors with ADCs is the heterogeneous expression of the target antigen (Ag), which however may be overcome by the so-called bystander killing effect. This unique, but still debated, feature of certain ADCs is represented by the unintentional payload diffusion from Ag-positive tumor cells to adjacent Ag-negative tumor cells. Some pharmacological characteristics, such as a hydrophobic payload or a cleavable linker, seem to play a major role in this effect.

Summary

Abundant preclinical evidence of the bystander effect has emerged, and the clinical activity of ADCs in tumors with a heterogeneous Ag expression suggests the relevance of this feature. Additional studies are required to investigate if the bystander effect is necessary for achieving a solid activity with ADCs.

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Authors and Affiliations

  1. Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, via G. Ripamonti 435, 20141, Milan, Italy

    Federica Giugliano, Chiara Corti, Paolo Tarantino & Giuseppe Curigliano

  2. Department of Oncology and Haematology, University of Milan, Milan, Italy

    Federica Giugliano, Chiara Corti, Paolo Tarantino & Giuseppe Curigliano

  3. Breast Oncology Center, Dana-Farber Cancer Institute, Boston, MA, USA

    Paolo Tarantino

  4. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Flavia Michelini

  5. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Flavia Michelini

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  1. Federica Giugliano
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  2. Chiara Corti
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  3. Paolo Tarantino
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  4. Flavia Michelini
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Correspondence to Paolo Tarantino.

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PT served as advisor/consultant for AstraZeneca. GC received honoraria for speaker, consultancy, or advisory rule from AstraZeneca, Roche, Pfizer, Novartis, Seattle Genetics, Lilly, Ellipses Pharma, Foundation Medicine, Daiichi Sankyo, and Samsung. The other authors declare no competing interests.

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Giugliano, F., Corti, C., Tarantino, P. et al. Bystander effect of antibody–drug conjugates: fact or fiction?. Curr Oncol Rep 24, 809–817 (2022). https://doi.org/10.1007/s11912-022-01266-4

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  • DOI: https://doi.org/10.1007/s11912-022-01266-4

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