Tci-gal-1 modulates apoptosis, degranulation, and production of cytokines by activated RBL-2H3 cells without detectable influence on gene transcription. This parasite protein is crucial for modulation of the protective immune response and the inhibition of chronic inflammation driven by mast cell activity.

Quantification of hemagglutination was shown to be optimal using U-bottom plates imaged and analysed with FIJI ImageJ rather than flat-bottom plates read for absorbance on an optical density plate reader. Galectin-3-induced red blood cell agglutination efficacy increased significantly from blood group O to A to B. However, for both the galectin-1 monomer and concatemer, a more comparable effect was observed between blood group B and O, but with more potent effects than in blood group A. Inhibition assays for both galectin-3 and galectin-1 induced-hemagglutination were able to demonstrate clear concentration responses and expected selectivity profiles for a set of small-molecule glycomimetics, confirming the historical profiles obtained in biochemical binding and functional cellular assays.

P2, N=0, Withdrawn, Providence Health & Services | N=92 --> 0 | Suspended --> Withdrawn

P1, N=36, Completed, Providence Health & Services | Active, not recruiting --> Completed | N=22 --> 36 | Trial completion date: May 2025 --> Oct 2022

P2, N=92, Suspended, Providence Health & Services | Trial completion date: Mar 2031 --> Jul 2031 | Trial primary completion date: Mar 2027 --> Jul 2027

Furthermore, in a murine model of PDAC, combined anti-galectin-9 and anti-PD-L1 treatment was associated with a greater decrease in tumor growth compared with treatment with either antibody therapy alone. Anti-PD-L1 antibody treatment for PDAC patients may be enhanced by inhibiting galectin-9.

P2, N=92, Suspended, Providence Health & Services | Trial completion date: Dec 2030 --> Mar 2031 | Trial primary completion date: Dec 2026 --> Mar 2027

Plant-derived carbohydrates GM-CT-01 and GR-MD-02 were used to inhibit extracellular Galectin-1/-3 binding to BCP-ALL cells in co-culture with stromal cells. Treatment with these compounds attenuated migration of the BCP-ALL cells to stromal cells and sensitized human BCP-ALL cells to vincristine and the targeted tyrosine kinase inhibitor nilotinib...Taken together, our results indicate a complicated joint contribution of Galectin-1 and Galectin-3 to BCP-ALL survival, with different roles for endogenous and stromal produced Galectins. These data indicate it will be important to efficiently block both extracellular and intracellular Galectin-1 and Galectin-3 with the goal of reducing BCP-ALL persistence in the protective bone marrow niche during chemotherapy.

in this study, high levels of Gal-1 and PLR were associated with poorer OS in SCLC patients, supporting their utility as clinical prognostic biomarkers. Moreover, the in vivo model suggests the inhibition of Gal-1 as a novel potential therapy for this disease with very poor prognosis.

P2, N=92, Suspended, Providence Health & Services | Trial completion date: Aug 2030 --> Dec 2030 | Trial primary completion date: Aug 2026 --> Dec 2026

Our findings reveal a regulatory axis for programmed death ligand 1 (PD-L1) expression in NPC cells, and targeting one component in this axis, Lgals1, is effective in boosting the immunogenicity of NPCs, providing a therapeutic avenue for treating NPC in clinic.

P1, N=22, Active, not recruiting, Providence Health & Services | Trial primary completion date: May 2022 --> May 2023

Changes in protein trafficking and the glycocalyx composition of cancer cells may explain the observed alterations in galectin expression. This study can be useful for the targeted selection of receptor tyrosine kinase and galectin inhibitor anti-cancer treatments.

While galectins are known to influence spatial organization and trafficking of this class of RTKs, no specific relationship has been elucidated between galectins -1 and -9 and FLT3. Our results indicate a potential interaction of clinical significance between FLT3 and galectins -1 and -9, the mechanism of which needs to be investigated further.

P2, N=92, Suspended, Providence Health & Services | Initiation date: Jan 2022 --> Jul 2022

This gene therapy targeting KRAS G12D mutation with a Gal-1 inhibition has a potential to modulate the oncogenic network and tumor microenvironment resulting in the repression of growth, metastasis, chemoresistance, and improvement in patient survival. This study will develop a novel sustainable therapeutic approach to target PDAC growth and improve patient survivability.

P1, N=22, Active, not recruiting, Providence Health & Services | Trial completion date: Oct 2021 --> May 2025 | Trial primary completion date: Oct 2021 --> May 2022

OTX008 decreased the viability of OSCC and NOK cells in a dose-dependent manner. The significant regulation of FOS suggests OTX008 causes early induction of the MAPK pathway via the immediate response gene FOS as a subunit of the AP-1 complex.

Hsa-miRNA-128-3p could be considered as a potential therapy for pancreatic cancer. We provided a new idea for targeted therapy of PDAC.

Galectin-1, which was commonly upregulated in preneoplastic lesions and tumors, emerged as a regulator of SCD1. Co-inhibitory treatment with PIK3CA inhibitors and the galectin-1 inhibitor OTX-008 resulted in synergistic cytotoxicity in human HCC cell lines, suggesting novel therapeutic venues.

In conclusion, our findings demonstrate that ibrutinib-resistant CLL cells exhibit a unique transcriptional pattern. The combination of LGALS1 and LAG3 expression could serve as an indicator of the sensitivity of ibrutinib and prognosis of CLL patients. LGALS1 inhibitor OTX008 helps to overcome ibrutinib-resistance of CLL cells.

P2, N=92, Suspended, Providence Health & Services | Initiation date: Aug 2021 --> Jan 2022 | Not yet recruiting --> Suspended

Importantly, we establish that galectin1 forms a complex with the transcription factor HOXA5 to reprogram the BTSC transcriptional landscape. Our data unravel an oncogenic signaling pathway by which the galectin1/HOXA5 complex maintains BTSCs and promotes glioblastoma.

P2, N=92, Not yet recruiting, Providence Health & Services

Finally, the sensitive 8505c line was xenografted in nude mice, and 3 weeks of OTX008 treatment (5 mg/kg/day) demonstrated a significant reduction in tumor and lung metastasize sizes without side effects. Overall, OXT008 showed significant anti-cancer effects both in vitro and in vivo in thyroid cancer lines expressing Gal-1, supporting further investigation of the molecular mechanisms of the drug and future clinical trials in patients with anaplastic thyroid cancer.

The same mechanism appeared to trigger the expression of VISTA protein, which acts as immunosuppressive receptor in T cells. Our results have therefore demonstrated that TGF-β1-induced signaling pathway can be considered as a potential highly efficient target for cancer immunotherapy.