Our Platform
IKT is developing an OV with the ability of (i) escaping NAbs, (ii) inducing tumor stroma destruction, thus improving the intravenous delivery efficacy, and (iii) activating T cell mediated killing of tumors.

Our objective is two-fold:​
  1. Secret the T-cell engager, CD3-scFv with FAP-scFv,  that destroys FAP+ cancer associated fibroblast, resulting in enhanced specific tumor infiltration and spread.

2.   Generate neutralization escape variant of  oncolytic vaccinia
      virus by genetically modifying multiple viral glycoproteins
      expressed on the surface of the virus. 
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Details Below
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Vaccinia Virus

  1. Advantages of our novel platform
  2. In comparison to other vaccinia viruses
  3. In comparison to BiTE antibodies
  4. Rationale for selecting vaccinia virus backbone

Advantages

The foremost perk of TEA-VV neutralization escape variant is its ability to escape anti-viral immune responses and kill tumor cells not infected with the virus.
We have successfully engineered the NEVs of VV with the ability of escaping anti-VV Nabs effectively. 
We have armed the VV with T-cell engager as a potential means of engaging T-cells for tumor destruction.
Targeting FAP+ cancer associated fibroblast promotes virus infiltration into and spread within the tumors.

​Superior to cytokine-producing VVs

  • The effectiveness of cytokines such as GM-CSF (JX594) depends on the immune system's antitumor responses
  • ​The inflammation produced by cytokines such as GM-CSF may increase viral clearance, reducing persistence of the oncolytic virus
  • Cytokines such as GM-CSF promote myeloid-derived suppressor cells, triggering protumor immune effects

What is BiTE?

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Structure of bi-specific t-cell engagers
BiTE stands for bispecific T-cell engager, a class of artifical bispecific monoclonal antibodies.A BiTE antibody is 
composed of two single chain variable fragments (scFv). A tumor-targeting scFv is combined with a T-cell activating ligand scFv. The opposing ends of the antibody bind tumor epitopes and T-cell receptors respectively. The resulting crosslinking causes T-cells to activate and release proteases and cytokines that destroy the tumor cell.

Beats Systemic BiTE Injection

TEA-VV induces local production of BiTE (bispecific T-cell engager) that might allow higher concentrations within tumors. Local production reduces systemic side effects such as flulike symptoms and CNS effects that would otherwise be caused by 
intravenous BiTE administration. With the knowledge of BiTE's short half-life, TEA-VV provides continual production of T-cell engagers, eliminating the need for continuous intravenous administration by infusion pumps and the hassle of BiTE manufacturing from mammalian producer cells.

Vaccinia Virus Backbone

​Multiple features make vaccinia virus an ideal backbone:
  • Long track record of safety with historical production and implementation of smallpox vaccine
  • Well-defined immune response
  • Sizable amount of clinical data available for reference
  • Large cloning capacity
  • Highly necrotic
  • Can be active in any tissue
  • Can be delivered systemically and spread to site of interest

References

  1. Giving oncolytic vaccinia virus more BiTE. Albelda SM1, Thorne SH2. Mol Ther. 2014 Jan; 22(1)6-8. http://www.ncbi.nlm.nih.gov/pubmed/24384909
  2. T-cell engager-armed oncolytic vaccinia virus significantly enhances antitumor therapy. http://www.ncbi.nlm.nih.gov/pubmed/24135899
  3. Combination of virotherapy and T-cell therapy: arming oncolytic virus with T-cell engagers​​. http://www.ncbi.nlm.nih.gov/pubmed/24333405

Selected Publications

  1. A simple and sensitive method for measuring tumor-specific T-cell cytotoxicity
  2. A Th1-inducing adenoviral vaccine for boosting adoptively transferred T-cells
  3. A20 is an antigen presentation attenuator, and its inhbition overcomes regulatory T-cell mediated suppression