Tumor-colonizing Salmonella: Chick Embryo Chorioallantoic Membrane (CAM) as In Ovo Model to Screen and Evaluate the Therapeutic Efficacy of Potential Vaccine Candidate Strains
Introduction
An attenuated Salmonella enterica serovar Typhimurium strain VNP20009 was employed in a phase I human clinical trial for evaluation in bacteria-mediated cancer therapy. This trial completely failed, demonstrating the challenges associated with the predictability of human translational success based solely on rodent studies.
Methods
In the current study, we explored and validated the applicability of an innovative in-ovo model: a naturally immune-deficient chick embryo chorioallantoic membrane (CAM) xenograft system to study the tumor colonizing process of Salmonella.
Results
Here we show that Salmonella Typhimurium preferentially colonizes tumors and directly causes tumor cell death in the transplanted CAM tumor model. Bacterial motility is not essential for tumor colonization or for intra-tumoral distribution. Both tumor colonization and invasion were independent of known virulence factors, as an extracellular lifestyle of Salmonella dominated in the CAM tumor model. However, an extracellular residence lifestyle of Salmonella did not require biofilm formation on the CAM-tumor. Evaluation of the VNP20009 strain in comparison to the wildtype parental strain in the CAM model showed inherently poor tumor colonization capability of the vaccine strain, irrespective of the host immune system.
Conclusion
These results highlighted the CAM as both an informative and predictive in vivo model for studying tumor colonizing mechanisms of Salmonella in an immunodeficient host, while also serving as an additional screening platform for testing the therapeutic efficacy of potential vaccine candidate strains.