title: A Fully Synthetic Self-Adjuvanting Globo H-Based Vaccine Elicited Strong T Cell-Mediated Antitumor Immunity.
abstract: Therapeutic cancer vaccines based on the abnormal glycans expressed on cancer cells, such as the globo H antigen, have witnessed great progress in recent years. For example, the keyhole limpet hemocyanin (KLH) conjugate of globo H has been on clinical trials as a cancer vaccine. However, such vaccines have intrinsic problems, such as inconsistence in eliciting T cell-mediated immunity in cancer patients and difficult quality control. To address the issue, a structurally defined fully synthetic glycoconjugate vaccine composed of globo H and monophosphoryl lipid A (MPLA) was developed. The new vaccine was shown to elicit robust IgG1 antibody responses and T cell-dependent immunity, which is desired for anticancer vaccine, and induce significantly faster and stronger immune responses than the globo H-KLH conjugate. Moreover, it was self-adjuvanting, namely, inducing immune responses without the use of an external adjuvant, thus MPLA was not only a vaccine carrier but also a build-in adjuvant. It was also found that antibodies induced by the new vaccine could selectively bind to and mediate strong complement-dependent cytotoxicity to globo H-expressing MCF-7 cancer cell. All of the results have demonstrated that the globo H-MPLA conjugate is a better cancer vaccine than the globo H-KLH conjugate under experimental conditions and is worth further investigation and development.
authors.affiliation: Department of Chemistry, Wayne State University, 1501 Cass Avenue, Detroit, Michigan 48202, United States.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Chemistry, Wayne State University, 1501 Cass Avenue, Detroit, Michigan 48202, United States.
authors.forename: Guochao
authors.initials: G
authors.lastname: Liao
authors.affiliation: Department of Chemistry, Wayne State University, 1501 Cass Avenue, Detroit, Michigan 48202, United States.
authors.forename: Satadru S
authors.initials: SS
authors.lastname: Mandal
authors.affiliation: Department of Chemistry, Wayne State University, 1501 Cass Avenue, Detroit, Michigan 48202, United States.
authors.forename: Sharad
authors.initials: S
authors.lastname: Suryawanshi
authors.affiliation: Department of Chemistry, Wayne State University, 1501 Cass Avenue, Detroit, Michigan 48202, United States.
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Guo
keywords: MCF-7 cancer cell; cancer vaccine; globo H; glycoconjugate; monophosphoryl lipid A