LAUSR

LAG3‐Ig as an immune adjuvant has elicited potent anti‐tumor immune responses in several preclinical and clinical studies, but the full potential immunostimulatory of LAG3‐Ig has yet to be achieved. We hypothesized that by anchoring LAG3‐Ig to the surface of liposomes, the adjuvant activity of LAG3‐Ig could be improved. We also investigated the immunotherapy by co‐delivery of liposome‐coupled LAG3‐Ig and P5 tumor antigen in mice model of TUBO breast cancer. We prepared and characterized novel PEGylated liposomes bearing surface conjugated LAG3‐Ig and P5. Consistent with our hypothesis, liposomes‐conjugated LAG3‐Ig via multivalent binding to MHC class II molecules exerted immunostimulatory of LAG3‐Ig and markedly induced maturation of dendritic cells more efficiently than free LAG3‐Ig. LAG3‐Ig‐P5‐immunoliposomes effectively elicited protective anti‐tumor responses more than locally injected soluble LAG3‐Ig + P5. The higher percentage of CD4+ and CD8+ T cells in the spleen and more rapid and pronounced infiltration of these effector cells into the site of the tumor were seen following immunoliposome therapy. Finally, anti‐tumor immunity induced by LAG3‐Ig‐P5‐immunoliposomes translated into the more tumor regression and prolonged survival of treated mice, compared to soluble immunotherapy. Taken together, our findings suggest that LAG3‐Ig‐P5‐immunoliposomes can be considered as a valuable candidate for developing a liposome‐based therapeutic cancer vaccine in treating HER2/ neu+ breast cancer patients.