Progress

EnGeneIC has invented methods by which a range of different drugs e.g. chemotherapeutic drugs Doxorubicin, Paclitaxel, Carboplatin, etc can be readily packaged within the EDVs.
EDVs can then be targeted to a specific cancer cell by attachment of a bispecific antibody or antibody fragment such as scFv. One end of the bispecific antibody attaches to the EDV and the other end is available for binding to a surface receptor
expressed by the cancer cell.
Once delivered inside the cell via endocytosis the EDVs are broken down in the late endosomes and the chemotherapeutic drugs released into the cytoplasm.
The drugs have been shown to remain bioactive and to be cytotoxic to the targeted cells.
This process is shown schematically in Figure 1.

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Figure-2 Click to Enlarge



Human tumor xenografts in mice treated with drug-packaged, targeted EDVs.
A series of in-vivo mouse xenograft studies where EDVs have been targeted intravenously and intra-tumorally to Her2 in breast and ovarian cancer xenografts, to EGFR in colon and breast cancer xenografts and to CD33 in leukemia xenografts have shown proof-of-concept of targeted drug delivery using EDVs.
Figure 2 illustrates targeted delivery of EDV-packaged Doxorubicin to a breast cancer xenograft in nude mice. There was highly significant tumor stabilization & regression of tumors (studied over 79 days) via EGFREDVsDox and no difference between intratumoural and intravenous delivery. When tumors treated with non-targeted EDVsDox (blue lines; G5 & G6) reached ~1000mm3 (day 63) and were then dosed with EGFREDVsDox (blue triangles on x-axis), there was dramatic tumor regression.

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Figure-3 Click to Enlarge



Treatment of Non-Hodgkin’s Lymphoma in dogs
Dogs suffering from Stage 4, T-cell Non-Hodgkin’s lymphoma were treated i.v. with canine CD3-targeted, Dox-packaged EDVs (canine CD3EDVsDox). CD3 is a normal T cell receptor.
Figure 3 shows the node measurements for Midori (40kg) throughout the canine CD3EDVsDox treatment. Results were achieved with 2,000-fold less Doxorubicin via the EDVs compared to conventional chemotherapy.

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