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Cancer therapy

Masking T cell engagers mitigates on-target off-tumor activity

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Clinical utility of T cell engagers (TCEs) in cancer immunotherapy for solid tumors is hampered by on-target off-tumor activity and dose-limiting adverse events. A study now proposes a solution to tackle these challenges through the design and preclinical characterization of extended half-life TCEs that are conditionally activated in the tumor microenvironment.

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Fig. 1: Mechanism of action of XPAT proteins.

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Author information

Authors and Affiliations

  1. Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA

    Aliyah B. Silver

  2. Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Aliyah B. Silver, Jeremy Wang & Jamie B. Spangler

  3. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA

    Jeremy Wang

  4. Department of Chemical and Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, USA

    Jamie B. Spangler

  5. Institute for NanoBioTechnology, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, USA

    Jamie B. Spangler

  6. Department of Materials Science and Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, USA

    Jamie B. Spangler

  7. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jamie B. Spangler

  8. Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jamie B. Spangler

  9. Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jamie B. Spangler

Authors
  1. Aliyah B. Silver
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  2. Jeremy Wang
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  3. Jamie B. Spangler
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Corresponding author

Correspondence to Jamie B. Spangler.

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The authors declare no competing interests.

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Silver, A.B., Wang, J. & Spangler, J.B. Masking T cell engagers mitigates on-target off-tumor activity. Nat Cancer 4, 439–441 (2023). https://doi.org/10.1038/s43018-023-00529-8

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  • DOI: https://doi.org/10.1038/s43018-023-00529-8

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