Montmorillonite-Based Oral Vaccine for Colorectal Cancer Immunotherapy through Mucosal Immune Activation

Mucosal cancer, a kind of malignancy originating in mucosal tissues and affecting various organs, such as colorectal cancer, is a major health challenge worldwide. Effective activation of mucosal immunity is crucial for its prevention and treatment. However, conventional vaccines administered subcutaneously or intramuscularly often fail to stimulate a robust immune response against mucosal cancer. In contrast, oral mucosal vaccines can harness the extensive mucosal surfaces of the gut for immune activation. Here, we developed an oral tumor therapeutic vaccine using manganese-rich montmorillonite nanosheets (Mn-MMT@OVA) with promising potential for colorectal cancer immunotherapy. Upon oral administration, the vaccine adheres to the intestinal mucosa and forms a vaccine depot that gradually releases antigens and Mn²⁺. These ions eliminate immune tolerance and activate robust mucosal immunity by cGAS-STING pathway stimulation. The mucosal imprinted effector immune cells migrate to the colonic mucosa and increase the level of cytotoxic T cell infiltration within the colorectal tumor via the mucosal homing effect, resulting in a marked inhibition of colorectal tumor growth. This work provides valuable insights into immune treatment against mucosal cancer and highlights the potential of oral mucosal tumor vaccines for therapeutic development.