Related Experiment Video
Updated: May 8, 2026
Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
Published on: April 26, 2024
Pharmacokinetics and antineoplastic activity of galectin-1-targeting OTX008 in combination with sunitinib
Massimo Zucchetti1, Katiuscia Bonezzi, Roberta Frapolli
1Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 20156, Milan, Italy.
Purpose:
OTX008 is a galectin-1-targeting compound, currently undergoing a phase I clinical trial. This study aimed at investigating OTX008 pharmacokinetics (PK) and antineoplastic activity.
Methods:
Pharmacokinetics and activity of OTX008 were analyzed in the human ovarian carcinoma A2780-1A9 and glioblastoma U87MG xenografted in nude mice. In vitro, OTX008 was tested on tumor and endothelial cells.
Results:
After 5 mg/kg i.v., OTX008 achieved plasma Cmax of 14.39 μg/mL, distributed rapidly, and was eliminated with a half-life of 31.4 h. Tumor OTX008 Cmax (1.65 μg/g, 1.76 μM), achieved at 0.5 h, remained high at 24 h (0.516 μg/g, 0.55 μM) with AUC of 15.76 μg/g*h. OTX008 accumulated in the tumor after repeated administrations achieving a concentration of 2.3 μM, compatible with the concentrations active in vitro. OTX008 (5 mg/kg i.v., every other day for 3 weeks) inhibited the in vivo growth of A2780-1A9, whereas U87MG was not sensitive. In vitro, OTX008 affected endothelial cell proliferation, motility, invasiveness, and cord formation. Tumor cell proliferation was also inhibited, with differences in sensitivity among cell lines (IC50 from 1 to 190 μM). OTX008 potentiated the activity of the tyrosine kinase inhibitor sunitinib on A2780-1A9 in vivo and in vitro, where the combination showed synergistic (endothelial cells) and additive (A2780-1A9) antiproliferative activity, indicating that the combination targets both the tumor and vascular compartments.
Conclusions:
OTX008-alone or in combination with sunitinib-has a favorable PK and antineoplastic activity on selected tumor models through the effects on both endothelial and tumor cells.
Insights
This study shows that OTX008, a galectin-1-targeting compound, has favorable pharmacokinetics and antineoplastic activity in ovarian cancer models. OTX008 demonstrated efficacy alone and in combination with sunitinib, targeting both tumor and endothelial cells.
Area of Science:
- Pharmacology
- Oncology
- Drug Development
Background:
- Galectin-1 is a target in cancer therapy.
- OTX008 is a novel galectin-1 inhibitor in clinical trials.
Purpose of the Study:
- To evaluate the pharmacokinetics (PK) and antineoplastic activity of OTX008.
- To assess OTX008's effects on tumor and endothelial cells in vitro and in vivo.
- To investigate the combination therapy of OTX008 with sunitinib.
Main Methods:
- Pharmacokinetic and activity studies were performed in A2780-1A9 ovarian carcinoma and U87MG glioblastoma xenografts in mice.
- In vitro assays assessed OTX008's effects on tumor and endothelial cell proliferation, motility, and invasiveness.
- Combination studies with sunitinib were conducted in vitro and in vivo.
Main Results:
- OTX008 exhibited favorable PK, with a half-life of 31.4 hours and significant tumor accumulation.
- OTX008 inhibited A2780-1A9 tumor growth in vivo and affected endothelial cell functions in vitro.
- The combination of OTX008 and sunitinib showed synergistic and additive antiproliferative effects, targeting both tumor and vascular compartments.
Conclusions:
- OTX008 demonstrates promising PK and antineoplastic activity against specific tumor models.
- OTX008's efficacy stems from its dual action on tumor and endothelial cells.
- Combination therapy with sunitinib enhances OTX008's therapeutic potential.
More Related Videos
15:04Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation
Published on: January 19, 2019
10:27Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
