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Comprehensive Surfaceome Profiling to Identify and Validate Novel Cell-Surface Targets in Osteosarcoma.

Yifei Wang1, Xiangjun Tian2, Wendong Zhang1

  • 1Department of Pediatrics, Children's Cancer Hospital, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Molecular Cancer Therapeutics
|March 21, 2022
PubMed
Summary

Researchers identified novel cell-surface targets for osteosarcoma (bone cancer) therapies. An MT1-MMP-targeted toxin conjugate showed promising antitumor activity in preclinical models, validating this approach for developing new cancer treatments.

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Area of Science:

  • Oncology
  • Proteomics
  • Transcriptomics

Background:

  • Immunoconjugates targeting cell-surface antigens are effective in various cancers.
  • Osteosarcoma lacks specific cell-surface targets for targeted therapies.

Purpose of the Study:

  • To identify and validate osteosarcoma-specific cell-surface antigens for therapeutic development.
  • To evaluate the therapeutic potential of targeting identified antigens.

Main Methods:

  • Integrated proteomic and transcriptomic surfaceome profiling to identify highly expressed osteosarcoma antigens.
  • Validation of target overexpression in osteosarcoma tissues.
  • Preclinical testing of an MT1-MMP-targeted toxin conjugate (BT1769) in patient-derived xenograft models.

Main Results:

  • Identified several cell-surface proteins highly expressed in osteosarcoma.
  • Validated overexpression of MT1-MMP, CD276, and MRC2 in osteosarcoma.
  • BT1769 demonstrated significant antitumor activity, high target affinity, and favorable pharmacokinetics in preclinical models.

Conclusions:

  • The surfaceome profiling approach successfully identifies novel, therapeutically relevant targets in osteosarcoma.
  • MT1-MMP is a promising target for developing novel osteosarcoma therapeutics.
  • Targeted toxin conjugates represent a viable therapeutic strategy for osteosarcoma.