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Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG

Yasuyuki Matsumoto1, Nan Jia1, Jamie Heimburg-Molinaro1

  • 1Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 3 Blackfan Circle, CLS-11090, Boston, MA, 02115, USA.

Scientific Reports
|March 28, 2023
PubMed

Insights

Researchers engineered an afucosylated antibody, Remab6-AF, to enhance anti-tumor activity. This modified antibody effectively targets Tn-positive cancers, showing potent efficacy in preclinical models.

Area of Science:

  • Immunology
  • Glycobiology
  • Oncology

Background:

  • Aberrant expression of the Tn antigen (CD175) on carcinomas correlates with poor patient outcomes.
  • Current anti-Tn antibodies may lack essential effector functions for effective cancer therapy.

Purpose of the Study:

  • To develop an afucosylated anti-Tn antibody with enhanced therapeutic potential.
  • To evaluate the efficacy of Remab6-AF in preclinical cancer models.

Main Methods:

  • Generation of afucosylated Remab6 (Remab6-AF) using FX gene-deleted HEK293 cells.
  • Assessment of antibody-dependent cell cytotoxicity (ADCC) in vitro.
  • Evaluation of tumor reduction in an in vivo xenotransplant mouse model.

Main Results:

  • Remab6-AF demonstrated potent ADCC activity against Tn-positive colorectal and breast cancer cell lines.
  • The afucosylated antibody significantly reduced tumor size in a preclinical mouse model.
  • FXKO HEK293 cells enabled the production of functionally enhanced antibodies.

Conclusions:

  • Afucosylation of Remab6 significantly enhances its anti-tumor effector function.
  • Remab6-AF represents a promising therapeutic candidate for Tn-positive tumors.
  • Targeting Tn antigen with engineered antibodies offers a viable strategy for cancer treatment.

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