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1187 Antibody-lectin bispecifics for glyco-immune checkpoint blockade
  1. Jessica Stark1,
  2. Melissa Gray1,
  3. Simon Wisnovsky1,
  4. Itziar Ibarlucea-Benitez2,
  5. Nicholas Riley1,
  6. Mikaela Ribi1,
  7. Marta Lustig3,
  8. Wesley Errington4,
  9. Bence Bruncsics5,
  10. Casim Sarkar4,
  11. Thomas Valerius6,
  12. Jeffrey Ravetch2 and
  13. Carolyn R Bertozzi1
  1. 1Stanford University, Stanford, CA, USA
  2. 2The Rockefeller University, New York, NY, USA
  3. 3Christian Albrechts University Kiel and University Medical Center Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany
  4. 4University of Minnesota, Minneapolis, MN, USA
  5. 5Budapest University of Technology and Economics, Budapest, Hungary
  6. 6Universitaetsklinikum Schleswig-Holstein UKSH, Kiel, Germany


Background Despite the curative potential of checkpoint blockade immunotherapy, a majority of patients remain unresponsive to existing treatments. Glyco-immune checkpoints – interactions of cell-surface glycans with lectin, or glycan binding, immunoreceptors – have emerged as prominent mechanisms of immune evasion and therapeutic resistance in cancer.

Methods Here, we describe antibody-lectin chimeras (AbLecs), a modular platform for glyco-immune checkpoint blockade. AbLecs are bispecific antibody-like molecules comprising a tumor-targeting arm as well as a lectin ‘decoy receptor’ domain that directly binds tumor glycans and blocks their ability to engage lectin receptors on immune cells (figure 1).

Results AbLecs elicited tumor killing in vitro via macrophage phagocytosis and NK cell and granulocyte cytotoxicity, matching or outperforming combinations of monospecific antibodies with lectin-blocking or glycan-disrupting therapies. Furthermore, AbLecs synergized with blockade of the ‘don’t eat me’ signal CD47 for enhanced tumor killing.

Conclusions AbLecs can be readily designed to target numerous tumor-associated antigens and glyco-immune checkpoint ligands, and therefore represent a new modality for cancer immune therapy.

Abstract 1187 Figure 1

Antibody-lectin chimeras for glyco-immune checkpoint blockade

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