Anti-cancer mucosal vaccines: Therapeutic efficacy against cancers growing in mucosal organs

In the last decade, the field of cancer immunotherapy based on tumor-specific vaccines and tumor-specific cytotoxic T lymphocytes (CTLs) has advanced rapidly. Many cancers present with metastases to mucosal sites such as the lung or gastrointestinal tract (GI) and primary or secondary tumors in those sites are the most common cause of cancer-related mortality in the western world. Yet, most, if not all, of the evaluated experimental vaccination protocols rely on parenteral immunizations. Parenteral immunization protocols rarely induce mucosal immune responses. In contrast, mucosal immunization commonly induces both systemic and mucosal immune responses. We suggest that induction of tumor-specific immunity through mucosal-based vaccines might be beneficial for the control of primary or secondary tumor growth in mucosal sites such as the lung or the GI tract. Mucosal (intranasal) immunization with peptide corresponding to a defined CTL epitope and the mucosal adjuvant cholera toxin (CT) can induce potent effector and memory CTL responses in lung, regional cervical lymph node and spleen cell populations [1]. This mucosal vaccine was as efficient as a very-potent dendritic cells-based parenteral vaccine in protection against a parenteral (subcutaneous) challenge with a tumor carrying the CTL epitope [1]. The antigen-presenting capabilities of NALT dendritic cells was enhanced by CT after nasal immunization with CTL epitope peptide and CT [2]. Mice were protected from lung metastases after challenge with the malignant B16 melanoma cells by intranasal immunization with CT and CTL epitope peptide. Although IL-1beta is a potent mucosal adjuvant when administered intranasally with protein antigens and peptides containing T-h, T-CTL and B cell epitopes [3-5], IL-1beta adjuvant activity was not as potent as that of CT when co administered with CTL epitope peptide.