Targeting Globo H with a Novel Antibody-Drug Conjugate for Cancer Therapy

3 June 2024
The study explores OBI-999, an antibody-drug conjugate (ADC) targeting a hexasaccharide called Globo H, which is highly present in various cancers and minimally in normal tissues, making it a promising candidate for cancer immunotherapy. OBI-999 combines a monoclonal antibody OBI-888 specific to Globo H with monomethyl auristatin E (MMAE), a synthetic antineoplastic agent.

The research methods involved assessing Globo H's presence in different human cancer cell lines and determining OBI-999's binding specificity and internalization capabilities using flow cytometry and confocal microscopy. The anti-tumor effectiveness of OBI-999 was examined in xenograft and patient-derived xenograft models, with pharmacokinetic parameters being evaluated in both normal and tumor-bearing mice.

Results indicated that OBI-999 selectively bound to cancer cell lines expressing Globo H, including those from breast, gastric, lung, and pancreatic cancers, and did not bind to non-expressing lines. The conjugate was found to internalize and reach endosomes and lysosomes within 2.5 to 5 hours, implying that MMAE is released in a lysosome-dependent manner. In vivo studies showed significant tumor growth inhibition in response to OBI-999 in a dose-dependent manner, with complete inhibition observed in pancreatic cancer models at higher doses. OBI-999 demonstrated similar serum stabilities to Adcetris across various species and accumulated at the tumor site over time, with the highest levels observed 168 hours post-treatment and significantly higher MMAE levels in tumor masses compared to other organs and serum.

The conclusion highlights that OBI-999's preclinical studies have shown its targeting specificity and anti-tumor efficacy in multiple Globo H positive cancer types and its prolonged retention at the tumor site, providing a foundation for its potential clinical use in targeted cytotoxic therapy for solid tumors.

How to Use Synapse Database to Search and Analyze Translational Medicine Data?

The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

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Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

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By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

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Click on the image below to go directly to the Translational Medicine search interface.

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