A personalized, oral Ty21a-based neoantigen vaccine consisting of eukaryotic expression plasmid encoding patient-specific tumor neoantigens that are immunogenic and unique to the patients tumor, with potential immunomodulating and antineoplastic activities. Upon oral administration of personalized neoantigen vaccine NECVAX NEO1, the patient-specific neoantigens elicit a specific and potent cytotoxic T-lymphocyte (CTL) response against tumor cells expressing these neoantigens. Ty21a is a live-attenuated Salmonella typhi strain oral typhoid vaccine that is modified and used to deliver the neoantigens-encoding plasmids to the gut-associated lymphoid tissue.