Tumor-targeted delivery of lnc antisense RNA against RCAS1 by live-attenuated tryptophan-auxotrophic Salmonella inhibited 4T1 breast tumors and metastasis in mice

Exploring the potential of Salmonella-mediated anti-sense RCAS1 RNA therapy in combatting aggressive breast cancer

“…In contrast to mice models, humans frequently encounter Salmonella bacteria and thus harbor bacteria-specific immunity. 5 The major caveat to Chandran et al.’s 1 study is the lack of investigational studies in prior Salmonella-exposed mice models. Investigating the effect of preexisting Salmonella-specific immunity on the efficacy of Salmonella-based therapies might offer significant insights into why such therapies have been met with little success in human clinical trials.…”

“…The study by Chandran et al. 1 is an innovative and multifaceted approach involving targeted delivery, RNA interference, live-attenuated bacteria, and the complex interplay in breast cancer evolution and metastasis. Salmonella-mediated long non-coding (lnc) antisense RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) RNA therapy showed a significant reduction in breast tumor volumes and completely arrested the metastatic lung lesions via mechanisms involving suppression of tumor-promoting genes, reduction in tumor-associated suppressor macrophages (TAMs), and efficient activation of T cell responses.…”

“…Salmonella-mediated long non-coding (lnc) antisense RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) RNA therapy showed a significant reduction in breast tumor volumes and completely arrested the metastatic lung lesions via mechanisms involving suppression of tumor-promoting genes, reduction in tumor-associated suppressor macrophages (TAMs), and efficient activation of T cell responses. 1 …”

“…This innovative Chandran et al. 1 study tackles cancer specificity by engineering the Salmonella Typhimurium (ST) strain and delivering antisense RNA to silence RCAS1 mRNA that is highly expressed in cancer cells and tumor tissues. 4 Both strategies could serve to increase target specificity while minimizing the effects on non-target tissues.…”

“…The Chandran et al. study 1 has successfully constructed a live-attenuated tryptophan-auxotrophic ST strain that selectively invades and propagates in cancer tissues ( Figure 1 ). This can be attributed to Salmonella’s ability to grow under low-oxygenated environments by harnessing the resources from the tumor microenvironment (TME).…”