Development of Globo-H conjugated bacteriophage Qβ mutant virus-like particles as an anticancer vaccine

Globo-H is a tumor-associated carbohydrate antigen (TACA) that is overexpressed in various cancers, making it a promising target for anticancer vaccine development. However, traditional conjugate vaccines, such as those linked to keyhole limpet hemocyanin (KLH) or cross-reactive material 197 (CRM197), have demonstrated limited clinical efficacy. To address this limitation, we developed an innovative vaccine candidate by conjugating chemoenzymatically synthesized Globo-H to a mutant of bacteriophage Qβ (mQβ) virus-like particle. The resulting mQβ-Globo-H conjugate elicited significantly higher levels of anti-Globo-H IgG antibodies in mice compared to both KLH-Globo-H and CRM197-Globo-H conjugates. Furthermore, the antibodies produced by the mQβ-Globo-H conjugate exhibited strong binding to MCF-7 breast cancer cells and triggered potent complement-dependent cytotoxicity (CDC) against these cancer cells. In contrast, negligible antibody binding and CDC effects were observed against normal MCF-10A breast epithelial cells. This new conjugate vaccine also produced robust humoral responses in rabbits, with the resulting antibodies exhibiting high selectivity for human breast cancer tissues. These findings underscore the clinical translational potential of the mQβ-Globo-H conjugate vaccine.