Abstract 2529: A monoclonal anti-Globo H antibody, VK9 can mediate CDC/ADCC and inhibit adhesion of Globo H+ cancer cells to extracellular matrix
2012; American Association for Cancer Research; Volume: 72; Issue: 8_Supplement Linguagem: Inglês
10.1158/1538-7445.am2012-2529
ISSN1538-7445
AutoresJung‐Tung Hung, Jing‐Yan Cheng, Chen‐Chi Wu, Alice L. Yu,
Tópico(s)Monoclonal and Polyclonal Antibodies Research
ResumoAbstract Globo H is a hexasaccharides expressed on many carcinomas including breast, pancreas, prostate, and stomach, with limited expression on normal tissue. Monoclonal antibodies against glycan, such as CH14.18 GD2-specific antibody, have been proven to be a promising strategy for cancer therapy. Here we evaluated the biological activity and potential application of VK9, a murine IgG3 anti-Globo H antibody. FACS analysis showed that VK9 bound to MCF7 cells in a dose dependent manner at 0.01 - 30 μg/mL. It does not bind to GH (-) cell lines, including AU565 and MDA-MB-231. The specificity of VK9 as determined by glycan array of 87 printed carbohydrates revealed binding of VK9 to three glycans (Globo H, BB4, and BB3) only, without reactivity to Gb5 or sialyl-Gb5. Investigation of the biological activity of VK9 showed no obvious effects on the proliferation of MCF7 cells. However, VK9 inhibited adhesion of MCF7 cell on fibronectin (83.5 ± 1.3%, p = 0.001) or laminin (70.5 ± 2.8%, p = 0.001), but not BSA (85.6 ± 0.2%, p = 0.08) or collagen IV (105.1 ± 2%, p = 0.37), when compared to IgG3 isotype control. Moreover, VK9 was able to mediate CDC against MCF7 cells. It could also induce ADCC of human IL-2 activated peripheral blood mononuclear cells at an E/T of 6.25-100. Furthermore, we cloned the Fab region of VK9 to generate a mouse-human chimeric anti-Globo H antibody, cVK9. The binding affinity of cVK9 was similar to VK9 at concentration range of 6.25 - 50 ug/mL by ELISA analysis. In conclusion, VK9 could not only mediate ADCC and CDC but also inhibit adhesion of MCF7 cell on fibronectin and laminin. Thus, VK9 have the potential as therapeutic antibody for Globo H expressing carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2529. doi:1538-7445.AM2012-2529
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