Viruses have long been used in medicine: inactivated viruses are used prophylactically to boost immunity against infectious diseases. More recently, they have been investigated as living vectors for eradicating cancers (oncolytic viruses) and chronic infections, such as hepatitis and human immunodeficiency virus. To date, however, such therapeutic viral vaccines have not been easy to apply—the viruses often do not readily infect cells for therapeutic effects. (Click here for company profile.)

BioVex founders Robert Coffin (left) and David Latchman.

Gareth Beynon, chief executive officer of BioVex, claims that his company has a viable solution in the form of the virus that causes common cold sores—herpes simplex virus (HSV) type 1. “HSV is a large and complex virus and not many people were working on it,” says Beynon. However, David Latchman and postdoctoral scientist Robert Coffin, while working at University College London, investigated the modus operandi of the virus and how it might be harnessed for medicine—and it is this intellectual property that now underpins BioVex.

Latchman and Coffin's appreciation of how HSV infects and commandeers host cells for its own devices allowed them to construct two platform vaccine technologies. In their OncoVEX system, HSV has been engineered so that it replicates in rogue cancer cells only. OncoVEX is injected directly into solid tumors, where it infects cancer cells, replicates in number, and bursts open the rogue cells—the basis of oncolytic viral vaccines. However, even though OncoVEX infects cancer cells better than do many other oncolytic vaccines, says Beynon, alone, it will not clear the cancer completely. So the researchers added genes encoding human immune-stimulating agents, beginning with GM-CSF. When injected into melanomas in mice, OncoVEXGM-CSF not only eliminated those tumors, but also shrank non-injected tumors on the other side of the body. Moreover, the vaccine appeared to re-educate the immune system to look out for future tumor growth. In theory, OncoVEXGM-CSF may not only help shrink cancers but also reduce the risk of metastasis, which leads to a poor prognosis for cancer patients.

HSV is a particularly valuable vector for the creation of vaccines because it can infect dendritic cells—the cells of the immune system that are key to detecting foreign proteins (antigens) and raising an appropriate immune response. However, wild-type HSV can “switch off” dendritic cells after infection, suppressing the host's ability to raise an immune reaction against the virus. In BioVex's second platform—ImmunoVEX—HSV's ability to inactivate dendritic cells has been eliminated, and the resulting virus can effectively re-educate the body's immune system to recognize foreign antigens. ImmunoVEX will be used as immunotherapy for metastatic cancers and chronic infectious diseases. Beynon says that this will have to be done ex vivo: patients will donate a blood sample, and their dendritic cells will be extracted, infected with ImmunoVEX carrying a few select tumor antigens, and re-introduced into the patients' bodies. In theory, the treatment should “re-sensitize” the body against cancer and chronic infections, which have become invisible to the host's immune system. Several other companies follow a similar approach, but use the entire cell extracts from tumors as the cancer vaccine (the patient-specific “autologous approach”). BioVex focuses on four or five crucial antigens—in its first product, a set implicated in most malignant skin cancers—providing a “generic,” and possibly more cost-effective, therapeutic strategy.

BioVex has sufficient funds to take its first vaccine, OncoVexGM-CSF, into phase 1/2 trials for the treatment of malignant melanoma and breast, colon, and head and neck cancers later in the year. On the back of the phase 1 results, BioVex intends to raise additional funding to launch phase 2 trials of OncoVexGM-CSF. Next year, the company plans to begin its first clinical trial with ImmunoVEX for the treatment of malignant melanoma. BioVex also intends to generate revenues from collaborations with pharmaceutical companies, such as Aventis (Strasbourg, France) and AstraZeneca (London), which are currently testing the company's vector platforms. LF