T-SIGn Technology

PsiOxus is developing novel cancer immunotherapy products with a particular focus upon oncolytic viruses for solid tumors. We aim to be the world-leading immuno-oncolytic virus company, delivering medicines of value to patients with cancer.

Our work is product and platform based with a focus on discovering and developing innovative oncolytic viruses for treatment of solid tumors. Our products utilize enadenotucirev, our proprietary first generation oncolytic virus and our proprietary platform technology for next generation oncolytic viruses, Tumor-Specific Immuno-Gene Therapy (T-SIGn).

The T-SIGn platform uses enadenotucirev as a gene delivery vector (Figure 1). Up to three transgenes can be inserted into a modified enadenotucirev virus without impacting the oncolytic potency or selectivity of the virus.

T-SIGn viruses are injected intravenously and circulate in the body until they reach both primary and metastatic tumor tissue. The T-SIGn viruses replicate only in tumor tissue and not within normal tissue. At the time of viral replication, the DNA encoded transgenes are transcripted into mRNA which in turn is translated into proteins. In effect, the T-SIGn virus turns the tumor cell into a “drug factory”. This results in localised delivery of biological agents that can enhance the activity of enadenotucirev through multiple known and/or novel mechanisms.

The T-SIGn viruses developed to date can be classified into one of four groups according to the transgenes expressed:

Cytokine or Chemokine armed enadenotucirev: here the transgenes encode for cytokines and/or chemokines secreted by the tumor cells. The aim is to modify the tumor micro-environment to enhance immune infiltration and activation (Figure 2.)

Antibody or antibody fragment armed Enadenotucirev: here the transgenes encode for secreted antibodies, antibody fragments or BiTe’s. The aim again is to modify the tumor micro-environment to enhance immune infiltration and activation (Figure 3.).

Membrane Integrated T-cell Engager (MiTe’s) armed viruses: here the transgenes encode for T-cell engaging ligands that are bound to the tumor cell membrane. The aim is to locally activate T-cells to kill tumor cells and mediate other immune effector mechanisms (Figure 4). NG-348 is the lead T-SIGn virus expressing MiTe’s.

Combination armed viruses: here the virus expresses some combination of cytokines, chemokines, antibodies and MiTe’s to produce a combination immunotherapeutic effect (Figure 5).

View the AACR 2016 poster on T-SIGn

View the AACR 2017 poster on T-SIGn

Figure 1 – Arming EnAd to Deliver Immuno-Therapeutics to Local Tumor Sites of Action

Figure 2. – Cytokine/Chemokine Armed Enadenotucirev: Cytokines and/or Chemokines

Figure 3. – Antibody armed Enadenotucirev (AbEnAd’s) = antibodies, antibody fragments or BiTe’s

Figure 4. – Membrane-integrated T-cell Engagers (MiTe) = T-cell Activating Ligands

Figure 5. – Combination Therapies: Combinations to Address Multiple Pathways

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