Tumor growth control with IDO-silencing Salmonella--letter.

Blache and colleagues (1) state "Although previous studies in mice have observedmodest tumor control with administration of attenuated Salmonella typhimurium (S. typhimurium) alone, it has proven to be less effective in more aggressive tumor models. Moreover, in clinical trials using the S. typhimurium strain VNP20009 for treatment of metastatic melanoma, minimal tumor S. typhimurium colonization was observed, which ultimately resulted in nomeasurable regression. Thus, improving S. typhimurium tumor colonization will likely enhance its therapeutic efficacy." The S. typhimurium A1-R strain developed by our laboratory has high tumor colonization efficacy and antitumor efficacy. S. typhimurium A1-R is auxotrophic for Leu-Arg, which prevents it from mounting a continuous infection in normal tissues. A1-R has no other attenuating mutations as does VNP20009 and, therefore, has very high tumor-targeting capability. A1-R was able to eradicate primary and metastatic tumors as monotherapy in nude mouse models of prostate, breast, lung, and pancreatic cancer, as well as sarcoma and glioma, all of which are highly aggressive tumormodels (2–11). The efficacy results obtained with S. typhimuriumA1-R suggest that the further steps to transform such a strain with IDOsiRNA, as done by Blache and colleagues (1) with VNP20009, may not be necessary to increase colonization. A direct comparison of tumor-targeting of the IDO-transformed S. typhimurium VNP20009 strain described by Blache and colleagues (1) and S. typhimurium A1-R would be enlightening.