NG-348 is PsiOxus’ first T-SIGn virus to be studied in human clinical trials.  NG-348 is designed to drive powerful T-cell immune responses locally within the tumor microenvironment. NG-348 uses an oncolytic adenoviral vector to deliver genes for two immunomodulatory membrane integrated T-cell proteins:

A membrane anchored full-length human CD80

A membrane anchored antibody fragment specific for the T-cell receptor CD3 protein

NG-348 is designed to be administered intravenously and to infect and replicate only in tumor cells.  Upon replication, those same tumor cells are simultaneously directed by the encoded genes to produce the two membrane anchored T-cell proteins locally. They are expressed together on the surface of NG-348 infected tumor cells and provide both the T-cell receptor and costimulatory activation signals to activate tumor-fighting T-cells (including the T-cells already present in the tumor, as well as T-cells recruited into the tumor in response to the virus infection) in an antigen independent manner. NG-348 is therefore designed to drive local T-cell immune responses selectively within the tumor microenvironment to kill cancer cells (Figure 1.).

In essence, this approach is the mirror image of CAR-T therapies, which require the patient’s T-cells be extracted and modified in an external setting, whereas NG-348 is an off-the-shelf product in which gene therapy modifies the tumor cells within the patient to then engage the patient’s T-cells to fight cancer in solid tumors (Figure 2.).

NG-348 infected tumor cells have been shown to potently activate both CD4 and CD8 human T-cells, in-vitro and in a human tumor xenograft in-vivo model, whereas non-tumor cells exposed to NG-348 did not show these effects.

In December 2017, it was announced that NG-348 was approved for use in human clinical trials.

View the AACR 2017 poster on T-SIGn

Figure 1. – NG-348 T-cell Activation Mechanism

Figure 2. – NG-348 versus CAR-T Therapy

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