Chemical synthesis and immunological evaluation of entirely carbohydrate conjugate Globo H-PS A1.
Samir GhoshKevin R TrabbicMengchao ShiSharmeen NishatPradheep EradiKristopher A KleskiPeter R AndreanaPublished in: Chemical science (2020)
An anticancer, entirely carbohydrate conjugate, Globo H-polysaccharide A1 (Globo H-PS A1), was chemically prepared and immunologically evaluated in C57BL/6 mice. Tumor associated carbohydrate antigen Globo H hexasaccharide was synthesized in an overall 7.8% yield employing a convergent [3 + 3] strategy that revealed an anomeric aminooxy group used for conjugation to oxidized PS A1 via an oxime linkage. Globo H-PS A1, formulated with adjuvants monophosphoryl lipid A and TiterMax® Gold. After immunization an antigen specific immune response was observed in ELISA with anti-Globo H IgG/IgM antibodies. Specificity of the corresponding antibodies was determined by FACS showing cell surface binding to Globo H-positive cancer cell lines MCF-7 and OVCAR-5. The anti-Globo H antibodies also exhibited complement-dependent cellular cytotoxicity against MCF-7 and OVCAR-5 cells.
Keyphrases
- immune response
- cell surface
- induced apoptosis
- breast cancer cells
- squamous cell carcinoma
- papillary thyroid
- oxidative stress
- cancer therapy
- cell cycle arrest
- single cell
- drug delivery
- fatty acid
- skeletal muscle
- cell proliferation
- inflammatory response
- gene expression
- endoplasmic reticulum stress
- squamous cell
- hiv infected
- silver nanoparticles