Abstract 4814: Specificity, biodistribution, tumor targeting, and pharmacokinetics of a novel humanized anti-Globo H antibody, OBI-888, for cancer immunotherapy

Abstract

Abstract Background: OBI-888 is a humanized monoclonal IgG1 antibody that binds to Globo H (GH), a tumor associated carbohydrate antigen. It is developed as a therapy to treat GH positive cancers. In the present study, we examined the binding specificity, binding epitope, antigen targeting ability, and pharmacokinetics (PK) of OBI-888. Methods: The binding specificity of OBI-888 was evaluated by cross-reactivity ELISA and titration ELISA with various glycans. Competition ELISA using various truncated structures of GH was conducted to identify the binding epitope of OBI-888. To confirm the antigen targeting ability, OBI-888 labeled with 111In via p-SCN-bn-DTPA chelator were IV injected in mice with tumor bearing GH positive MCF7 cells and no-tumor bearing. 111In-DTPA-OBI-888 at 32 μCi/4 μg and 400 μCi/16 μg were injected for biodistribution and MicroSPECT imaging studies, respectively. PK profile of OBI-888 was evaluated in non-tumor bearing nude mice at 5 mg/kg of OBI-888 via IV injection (n=5). Results: OBI-888 demonstrated specific binding to GH, with minimal cross reactivities to the other 25 types of glycan tested. Among the Globo series antigens, such as SSEA-3-ceramide and SSEA-4-lipid, OBI-888 showed specific binding to GH-ceramide. In addition, OBI-888 does not bind to truncated structures of GH and instead, requires a full hexasacharide structure of GH. Biodistribution study showed that 111In-OBI-888 was preferentially localized to the tumor site. The uptake of In111-OBI-888 in MCF7 tumor plateaued at 11.71±2.38 %ID/g at 24-hour post injection and remained at similar levels until 72-hour post injection. The tumor/muscle ratio peaked at 11.26±1.90 %ID/g at 72-hour post injection. Besides highly concentrated in the tumor sites, the dynamics and extent of distributions of OBI-888 in various organs of the tumor-bearing mice were comparable to that of non-tumor bearing mice. The radioactivity accumulation of In111-OBI-888 in liver, spleen and kidneys were approximately 10% ID/g at 1 h postinjection and decreased to about 5% ID/g at 24 h postinjection. MicroSPECT imaging studies confirmed the localization of 111In-OBI-888 at the tumor site of MCF7 bearing mice. PK parameters were concluded as follows: half-life (T1/2) = 5.1 days; estimated clearance (CL): 29.1 mL/d/kg; steady state volume of distribution (Vss): 179.3 mL/kg. Conclusions: The present study identified the epitope of OBI-888 and demonstrated its binding specificity. The observed biodistribution and microSPECT results demonstrated OBI-888’s specific targeting to GH positive tumor cells. Pharmacokinetic profiles showed acceptable half-lives in mice. Overall, the pre-clinical data support a first-in-human trial in cancer immunotherapy. Moreover, our findings indicate that the OBI-888 has the potential to be developed into a diagnostic agent for imaging GH-expressing cancers. Citation Format: Yu-Chi Chen, Ming-Chen Yang, Chi-Sheng Shia, Chun-Yen Tsao, Jiann-Shiun Lai, I-Ju Chen. Specificity, biodistribution, tumor targeting, and pharmacokinetics of a novel humanized anti-Globo H antibody, OBI-888, for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4814.