Scientists apply oncolytic adenovirus programmed by synthetic gene circuit to tumor immunotherapy

Recently, Tsinghua University and other researchers published the title of "online adenovirus program by synthetic gene circuit for cancer" on nature communications In this paper, we use the synthetic gene circuit to program oncolytic virus, which improves the specificity of oncolytic virus treatment, realizes the controllable and local expression of immune effector, and is expected to become a treatment strategy for a variety of cancers Oncolytic virus is a kind of tumor killing virus with replication ability Through gene transformation of some viruses with weak pathogenicity in nature, a special oncolytic virus is produced By using the inactivation or defect of tumor suppressor gene in the target cell, tumor cells can be selectively infected, in which a large number of tumor cells can be reproduced and eventually destroyed At the same time, it can stimulate the immune response, attract more immune cells to continue to kill the residual cancer cells Different from traditional drugs with clear pharmacokinetics and pharmacodynamics, the results of immunotherapy with oncolytic virus depend on the population dynamics and interaction of tumor cells, viruses and peripheral immune cells Because it is difficult to improve the specificity and immune response to cancer, and the understanding of population dynamics is limited, how to improve the efficacy of oncolytic virus therapy is still a challenge In this study, researchers have constructed a controllable and modular synthetic gene circuit, which can selectively control the replication of adenovirus and the release of immune effectors in HCC cells according to the input of different promoters and microRNA Through mouse model experiment and computer simulation, researchers found that replication adenovirus has better antitumor effect than non replication adenovirus In the immunoactive mice model, it can be observed that the combination of tumor lysis and the secretion of immunomodulators can produce synergistic effects on the local lymphocyte toxicity and the improvement of systemic immunity In addition, the computational simulation of this study shows that the oncolytic virus encoding immunomodulator has better therapeutic effect than the combination of oncolytic virus and immune effector This study provides an effective design method of oncolytic adenovirus, which is expected to be used in many cancer immunotherapy.