Escherichia coli Nissle 1917 secreting functional interleukin 2 targets tumours and enhances the immune response to suppress tumours [post]

Binghua Lu, Huijun Yang, Fei Liu, Yunjun Sun, Haocheng He, Xuezhi Ding, Shengbiao Hu, liqiu xia
2020 unpublished
Escherichia coli Nissle 1917 (EcN) is non-pathogenic probiotic bacteria. Previous studies have indicated that EcN can accumulate and proliferate selectively in solid tumours in BALB/c mouse models. In this study, EcN was engineered to express human interleukin 2 (hIL-2), which is known to enhance immune responses to tumours by activating a variety of immune cells. IL-2 expressed by EcN was proven to activate PBMCs in vitro. Compared to control EcN, intraperitoneally injected EcN expressing
more » ... EcN expressing hIL-2 (EcN(hIL-2)) was selectively distributed in the tumour microenvironment and inhibited the growth of CT26 tumours in a tumour-bearing mouse model. Antitumour activity was achieved without toxicity to key normal organs and tissues, such as liver, spleen and kidneys. The antitumour mechanism was associated with the infiltration of inflammatory cells, such as T cells, neutrophils and macrophages. These findings provide evidence that the combination of tumour-targeting EcN bacteria and delivery of the immunostimulatory factor IL-2 can be exploited as a promising tumour immunotherapy.
doi:10.21203/rs.3.rs-27294/v2 fatcat:mxn2obpvrfbenelpr2y7kj4gtm