Immunoengineering can overcome the glycocalyx armour of cancer cells

Sangwoo Park1,2, Marshall J Colville1,2, Justin H Paek3

  • 1Field of Biophysics, Cornell University, Ithaca, NY, USA.

Nature Materials
|February 16, 2024
PubMed

Insights

Cancer cells shield themselves from immune attack using their glycocalyx. Reducing glycocalyx thickness or engineering immune cells can enhance natural killer cell-mediated cytotoxicity against cancer.

Area of Science:

  • Cancer Biology
  • Immunology
  • Biophysics

Background:

  • The cancer cell glycocalyx acts as a barrier against immune surveillance.
  • Understanding the molecular regulation of glycocalyx physical properties is crucial for overcoming immune evasion.

Purpose of the Study:

  • To investigate how cancer-associated mucins and their glycosylation influence glycocalyx thickness.
  • To determine the impact of glycocalyx thickness on immune cell interactions and cytotoxicity.
  • To explore immunoengineering strategies to enhance anti-cancer immunity.

Main Methods:

  • Analysis of cancer-associated mucins and their glycosylation.
  • Measurement of glycocalyx nanoscale material thickness.
  • Assays for natural killer cell-mediated cytotoxicity.
  • Engineering of effector cells with chimeric antigen receptors and glycocalyx-editing enzymes.

Main Results:

  • Cancer-associated mucins and their glycosylation determine glycocalyx thickness.
  • Natural killer cell-mediated cytotoxicity is inversely correlated with glycocalyx thickness.
  • A ~10 nm change in glycocalyx thickness significantly impacts susceptibility to immune attack.
  • Enhanced stimulation of natural killer and T cells via chimeric antigen receptors improves cytotoxicity against mucin-expressing cells.
  • Engineering effector cells with mucinases and sialidases enhances cytotoxicity.

Conclusions:

  • The glycocalyx serves as a physical barrier contributing to cancer immune evasion.
  • Immunoengineering strategies, including glycocalyx editing and enhanced immune cell stimulation, can overcome this barrier.
  • Targeting the cancer cell glycocalyx offers a promising approach for cancer immunotherapy.

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