Date: 2016-10-05
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the 10th International Meeting on Replicating Oncolytic Virus Therapeutics, Vancouver,
Company: Transgene (France)
Product:
Action
mechanism: oncolytic virus/intrabody.
Disease:
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On October 5, 2016, Transgene presented an approach to improve the cytotoxic activity of oncolytic viruses at the 10th International Meeting on Replicating Oncolytic Virus Therapeutics, Vancouver, Canada October 1–4, 2016. This approach is based on the use of intrabodies, fragments of recombinant monoclonal antibodies designed to act intracellularly and to bypass a mechanism which prevents viral-induced cytolysis that is seen in some resistant tumor cell lines. These results open new possibilities for engineering the next generation of oncolytic viruses. The research was conducted with an oncolytic virus candidate, based on the Copenhagen strain of the vaccinia virus (VACV), displaying two key mutations that confer tumor selectivity (TK- and RR-). In the poster, scientists from Transgene and collaborating academic institutions describe the potential of a new approach in designing an oncolytic virus. The research identifies 16 key tumor cell components produced in response to VACV infection, which are implicated in resistance. It also outlines the ability of the construct to express a monoclonal antibody called an “intrabody” in tumor cells, that is able to selectively neutralize one of these tumor cell components by binding to it and re-localizing it into the cell nucleus where it cannot be activated. This relocalizing aims to achieve the same effect as siRNA knockdowns. The research was undertaken in several tumor cell lines that have low susceptibility to VACV-induced cytolysis. These promising results broaden the scope of possible cancer indications that can be targeted using oncolytic viruses. Transgene intends to create a new generation of improved oncolytic virus based therapeutics VACVs capable of intrabody-mediated relocalizing of tumor cell proteins and as a result to enhance cancer killing. Transgene’s lead oncolytic viral therapeutic Pexa-Vec is in a phase 3 trial evaluating its potential as a novel treatment for patients with hepatic cell carcinoma. The Phase 3 trial is being conducted by Transgene’s partner SillaJen. Transgene is planning to conduct further trials with Pexa-Vec in combination with immune checkpoint inhibitors in patients with solid tumors. The second advanced product is TG6002, a second generation of oncolytic virus, is expected to enter Phase 1 trial in H1 2017 in patients with glioblastoma. This study will be conducted at AP-HP with Pr. Delattre as principal investigator, with the support of InCa (French National Cancer Institute). TG6002 is based on the Copenhagen strain of the vaccinia virus (VACV), which has had the TK and RR genes deleted to prevent it from replicating in normal cells. It has also been designed to express the FCU1 gene allowing it to be used in combination with 5FC to locally produce 5 FU, a commonly used chemotherapeutic agent.
