PT  - JOURNAL ARTICLE
AU  - Stark, Jessica
AU  - Gray, Melissa
AU  - Wisnovsky, Simon
AU  - Ibarlucea-Benitez, Itziar
AU  - Riley, Nicholas
AU  - Ribi, Mikaela
AU  - Lustig, Marta
AU  - Errington, Wesley
AU  - Bruncsics, Bence
AU  - Sarkar, Casim
AU  - Valerius, Thomas
AU  - Ravetch, Jeffrey
AU  - Bertozzi, Carolyn R
TI  - 1187 Antibody-lectin bispecifics for glyco-immune checkpoint blockade
AID  - 10.1136/jitc-2023-SITC2023.1187
DP  - 2023 Nov 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - A1307--A1307
VI  - 11
IP  - Suppl 1
4099  - http://jitc.bmj.com/content/11/Suppl_1/A1307.short
4100  - http://jitc.bmj.com/content/11/Suppl_1/A1307.full
SO  - J Immunother Cancer2023 Nov 01; 11
AB  - 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