Vemuri, S. (2020). Glycovariants of the novel immunotherapeutic drug ManC-lectibody and their effects on ADCC activity. The Young Researcher, 4 (1), 148-163.
Existing cancer treatments have detrimental side effects that stem from drugs’ inability to distin- guish between healthy and cancerous cells. Scientists have researched immunotherapy, an alternative treatment which essentially enhances the innate immune system to eliminate diseased cells. ManC-lectibody is a novel immunotherapeutic drug that imitates an antibody and performs a process known as antibody-dependent cell-mediated cytotoxicity or ADCC within the humoral immune system. Previous research proves that ManC-lectibody is highly selective to oligomannose glycans, or sugars which are expressed along the surface of a cancer cell. Additionally, ManC-lecti- body has been known to induce ADCC but there is no information regarding modifications to the drug’s structure and how those modifications can influence ADCC activity. This study aims to find what glycovariants of ManC-lectibody will increase ADCC activity. It was hypothesized that the GnGn glycovariant, a humanized Fc glycosylation modification, would increase ADCC activity. An ADCC reporter assay served as the primary method for the research and quantified ADCC activity. Three glycovariants of ManC-lectibody were created: GnGn, Wild type, and N200Q. A dose re- sponse curve was created to measure the efficacy and potency of the glycovariants of the drug. The GnGn glycovariant of ManC-lectibody was the most efficacious against lung cancer cells (LLC cell line) but was the most potent against melanoma cancer cells (B16F10 cell line). A two-way ANOVA statistical test proved that the GnGn glycovariant was statistically significant and produced a strong effect against the lung, melanoma, and ovarian cancer cells, therefore indicating that the GnGn glycovariant makes the ManC-lectibody a more effective drug.
Keywords: ManC-lectibody, antibody-dependent cell-mediated cytotoxicity (ADCC), fragmented crystallizable region (Fc region), Fc receptors, lung cancer, ovarian cancer, melanoma