Food-Grade Bacteria Engineered to Secrete Cancer Peptide Vaccine Trigger Immune Response Against Colorectal Cancer in Mice

Two signal peptides (SPK1 and SPKM19) were used to express and secrete KRAS oncopeptides from L. lactis NZ9000. Expression and secretion efficiency were compared in vitro. BALB/c mice were orally immunized, and mucosal immune responses were assessed by measuring KRAS-specific IgA antibodies in intestinal washes.

Colorectal cancer is the third most common cancer worldwide, and KRAS mutations are present in approximately 40% of cases. Current immunotherapies (checkpoint inhibitors) have limited effectiveness in most colorectal cancers. An oral vaccine that trains the gut immune system to recognize KRAS-mutant cancer cells could provide a non-invasive, targeted immunotherapy approach. Using food-grade bacteria as the delivery vehicle makes this potentially safer and more scalable than traditional vaccine platforms.

KRAS-targeted vaccines are one of the most active areas in cancer immunotherapy, with several peptide vaccines in clinical trials. Most use traditional injection-based delivery, but oral mucosal vaccines could be particularly advantageous for gastrointestinal cancers where the immune response needs to be primed at the site of disease. L. lactis-based vaccine delivery is a growing field — these bacteria are safe, can be produced cheaply, and naturally interact with the gut immune system. The finding that signal peptide performance is cargo-dependent is an important engineering lesson for this platform.

The study demonstrated immune response (IgA production) but did not assess whether this response actually prevents or treats colorectal tumors in an animal cancer model. IgA alone may be insufficient for anti-tumor immunity — T cell responses were not measured. The mouse immune system differs from humans. L. lactis does not colonize the gut, so repeated dosing would likely be required. The secretion yields and resulting antigen levels at the mucosal surface were not quantified in sufficient detail to predict human immunogenicity.