Immunomodulation of Globo-H antigen using Gold Nanoparticles for Breast Cancer Therapy

Abstract

Cancer is a devastating disorder and till now no medicines or therapies beaten down its spreading. Tumor associated carbohydrate antigens (TACAs) are unique antigen signatures on cancer cell surface to develop markers to target cancer cells. However, owing to their poor immunogenicity, most of the TACA as such failed to induce T-cell mediated immunity. Previously, Danishefsky et al. used KLH (keyhole limpet hemocyanin) as a carrier protein to improve the immunogenicity of TACAs. However, the TACA-KLH conjugate induced T-cell independent immune responses and produced high level of antibodies against KLH, compared to TACAs. To avoid antibody against the platform and to induce cytotoxic T-cell mediated immune responses, Herein, we proposed to conjugate TACAs on gold nanoparticles to increase the high titre IgG antibody against specific TACAs. We have used gold nanoparticles of different shapes and size as adjuvants to alter the immune responses. As a prototype, we synthesized Globo-H active tetrasaccharides, a TACA found mainly on the breast cancer cell surfaces. We believe that multivalent glyco-nanoparticles are expected to produce high level of IgG antibody against TACA for targeting breast cancer cell for immunotherapy.