Camouflaging attenuated Salmonella by cryo-shocked macrophages for tumor-targeted therapy

Camouflaging attenuated Salmonella by cryo-shocked macrophages for tumor-targeted therapy

10 January 2024 | Leyang Wu, Zengzheng Du, Lin Li, Liyuan Qiao, Shuhui Zhang, Xingpeng Yin, Xiaoyao Chang, Chenyang Li and Zichun Hua
This study presents a novel approach to enhance the safety and efficacy of live bacterial therapies for cancer treatment by using cryo-shocked macrophages to deliver attenuated *Salmonella typhimurium* VNP20009. The researchers developed a method to load macrophages with live bacteria, which then underwent liquid nitrogen cold shock to preserve their cellular structure while eliminating pathogenicity. This "Trojan horse" strategy reduces the immunogenicity of the bacteria, avoiding neutrophil recruitment and activation, and enhances tumor targeting and bacterial survival. The engineered macrophages maintain high bacterial loading ( approximately 257 live bacteria per 100 cells) and retain the ability to release and proliferate intracellular bacteria. In a subcutaneous H22 tumor model, the LNT MACS/VNP cells showed significantly improved antitumor efficacy compared to other groups, including reduced tumor growth, increased tumor-infiltrating immune cells, and enhanced antitumor immune responses. The study highlights the potential of this strategy for expanding the therapeutic applications of live bacteria in cancer treatment.This study presents a novel approach to enhance the safety and efficacy of live bacterial therapies for cancer treatment by using cryo-shocked macrophages to deliver attenuated *Salmonella typhimurium* VNP20009. The researchers developed a method to load macrophages with live bacteria, which then underwent liquid nitrogen cold shock to preserve their cellular structure while eliminating pathogenicity. This "Trojan horse" strategy reduces the immunogenicity of the bacteria, avoiding neutrophil recruitment and activation, and enhances tumor targeting and bacterial survival. The engineered macrophages maintain high bacterial loading ( approximately 257 live bacteria per 100 cells) and retain the ability to release and proliferate intracellular bacteria. In a subcutaneous H22 tumor model, the LNT MACS/VNP cells showed significantly improved antitumor efficacy compared to other groups, including reduced tumor growth, increased tumor-infiltrating immune cells, and enhanced antitumor immune responses. The study highlights the potential of this strategy for expanding the therapeutic applications of live bacteria in cancer treatment.
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