GMMA decorated with mucin 1 Tn/STn mimetics elicit specific antibodies response and inhibit tumor growth
Elisa Pesce, Andrea Sodini, Elena Palmieri, Silvia Valensin, Cristina Tinti, Marco Rossi, Antonella De Rosa, Marco Fragai, Francesco Papi, Chiara Cordiglieri, Francesco Berti, Renata Grifantini, Francesca Micoli, Cristina Nativi
Abstract
Carbohydrate-based therapeutic vaccines are actively pursued as targeted immunotherapy to treat cancer. Aberrant glycosylation is indeed of paramount importance in tumors, leading to the formation of "neo-epitopes", known as tumor-associated carbohydrate antigens (TACAs), crucial in cancer onset, development and spread. Accordingly, the over-simplified mucin-type O-glycans Tn and STn have been confirmed among the most promising candidates for the development of cancer vaccines. In this work, we first propose genetically manipulated bacteria outer membrane vesicles (OMVs), namely GMMA, as a vaccine formulation platform to display glycan antigens. GMMA were glycosylated with multiple copies of structurally locked Tn mimetic or STn mimetic as cancer vaccine prototypes. These constructs, in non-adjuvanted formulations, showed sounding immunogenic properties in vivo and impressive efficacy in a mouse model of aggressive triple-negative breast cancer. This example of tailor-made therapeutic vaccine might revolutionize the approach to cancer therapy.