ICB can block the signal of immunosuppressed tumor by targeting receptors or matching physical checkpoint proteins (such as PD- 1/PD-L 1, CTLA-4) and restore the anti-tumor immune response. A large number of experiments show that compared with the standard treatment of various solid tumors, ICB antibody has been proved to be significantly improved in objective remission rate and survival time, whether used alone or in combination.
However, it cannot be ignored that most patients do not respond to ICB. In addition, the factors that control the successful elimination of immune-mediated tumor cells during ICB treatment are not completely clear, and scientists continue to study clear biomarkers that can predict the tumor response to ICB.
However, there is evidence that ICB has the greatest benefit in tumors with high levels of tumor infiltrating lymphocytes (TILs), high mutation load and increased expression of PD-L 1, that is, it has the strongest anticancer effect.
These reactive tumors are called immune "hot tumors"; In contrast, it is a "cold tumor" that lacks response. Studies have shown that these "cold tumors" cannot be treated with ICB, mainly due to the lack of tumor-associated antigen (TAAs) expression and/or presentation, low TILs density, the infiltration of inhibitory immune cell subsets (such as neutrophils, macrophages, regulatory T cells, myeloid inhibitory cells and natural killer cells), and immunosuppressive substances (such as IL- 10 and indoleamine-).
However, although a series of armless and armless oncolytic viruses have been verified for their selective targeting to tumors, the efficacy of using these viruses alone is always limited both before and in clinic.
So far, only one oncolytic virus has been approved to be listed in the United States and Europe at the same time, that is, Amgen's T-VEC for the treatment of advanced melanoma. T-VEC is an oncolytic virus based on herpes simplex virus 1 (HSV- 1), which has been modified to preferentially target tumor cells. This specificity is achieved by deleting the gene RL 1 encoding ICP34.5, which can prevent the virus from replicating in normal cells. At the same time, the developers also stimulated or enhanced the anti-tumor immune response by making the virus express human granulocyte-macrophage colony stimulating factor (GM-CSF).