# Extended half-life GlyTR1 combined with checkpoint blockade for Cancer Immunotherapy > **NIH NIH R42** · GLYTR THERAPEUTICS, INC. · 2023 · $400,000 ## Abstract Abstract Treatment of non-resectable recurrent/metastatic solid cancers is currently palliative only and there is an urgent unmet need for novel mechanisms of action and additional paradigm shifting therapeutic options. Antigen- targeting cancer immunotherapies such as bi-specific antibodies (eg Bi-specific T cell engager or BiTE’s) provide a unique approach for cancer immunotherapy. However, applying this therapeutic tactic to solid cancers has been restricted by a limited number of protein antigens safe for targeting. Moreover, even if safe cell-surface antigens are identified, different bi-specific antibodies will likely be needed for each different antigen/cancer. This would greatly increase development time and costs. Thus, there remains a great need for additional safe antigen- specific immunotherapies, particularly for those with refractory/metastatic solid cancers who have few therapeutic options. Many cell surface cancer-specific antigens are not proteins but rather complex carbohydrates that have limited or no expression in normal tissues. For example, β1,6GlcNAc-branched N- glycans constitute a small subset of the complex-type N-glycans expressed at the surface of normal human cells but are markedly up-regulated in diverse solid cancers by driver mutations in the receptor tyrosine kinase/RAS/phosphoinositide-3-kinase(PI3K) signaling pathway. Aberrant over-expression of β1,6GlcNAc- branched N-glycans in solid tumors drives RTK signaling, tumor growth, motility, invasion, and metastasis. As both a marker and driver of many diverse cancers, β1,6 GlcNAc-branched N-glycans provide an excellent target for antigen-specific immunotherapies. However, an antibody to β1,6GlcNAc-branched N-glycans has never been generated. To address this issue, we generated a novel class of immunotherapeutics that readily target abnormal glycan antigens with high specificity. We have termed this technology ‘Glycan-dependent T cell Recruiter’ (GlyTR, pronounced ‘glitter’). With funding from the Biden Cancer Moonshot program of the National Cancer Institute, we developed and optimized the GlyTR1 bi-specific protein that binds both β1,6GlcNAc-branched N- glycans and CD3 in T cells. The GlyTR1 bi-specific protein induces T cell-dependent killing of a wide diversity of solid cancers in vitro and in vivo with EC50’s as low as ~50 femtomolar, yet does not kill normal cells or trigger “on-target, off-cancer” toxicity in humanized mouse models. GlyTR1 is undergoing late-stage IND-enabling studies and upon FDA approval, the UC Irvine Cancer Center will perform a dose-escalation Phase 1 clinical trial in relapsed/metastatic solid cancer. However, as GlyTR1 has a short half-life of ~2.5hrs and requires constant intravenous infusion, herein we propose to develop a longer half-life version of GlyTR1. We also propose to examine for potential additive/synergistic activity with checkpoint inhibitors. Data from this proposal will be used to inform future clinical trials following... ## Key facts - **NIH application ID:** 10766646 - **Project number:** 1R42CA285234-01 - **Recipient organization:** GLYTR THERAPEUTICS, INC. - **Principal Investigator:** Michael Demetriou - **Activity code:** R42 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2023 - **Award amount:** $400,000 - **Award type:** 1 - **Project period:** 2023-09-21 → 2024-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10766646 ## Citation > US National Institutes of Health, RePORTER application 10766646, Extended half-life GlyTR1 combined with checkpoint blockade for Cancer Immunotherapy (1R42CA285234-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10766646. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*