Treatment of cancer by infusion of oncolytic herpes simplex virus to the blood

Abstract

An oncolytic herpes simplex virus is disclosed for use in a method of treating cancer in a human subject, the method comprising administering to the human subject at least one dose of oncolytic herpes simplex virus by infusion to the blood, wherein the oncolytic herpes simplex virus reaches cells of the cancer in which it replicates.

Description

RELATED APPLICATIONS[0001]This application is a continuation of U.S. patent application Ser. No. 15 / 875,858, filed Jan. 19, 2018, which is a continuation of International Patent Application No. PCT / GB2016 / 052177, filed Jul. 19, 2016, which claims priority to and the benefit of United Kingdom patent application No. 1512723.6 filed on 20 Jul. 2015 and United Kingdom patent application No. 1523091.5 filed on 30 Dec. 2015. The entire contents of each of these applications are incorporated herein by reference.FIELD OF THE INVENTION[0002]The present invention relates to methods of treatment of human cancers involving administration of an oncolytic herpes simplex virus to a human subject by infusion of the virus to the blood.BACKGROUND TO THE INVENTION[0003]Oncolytic virotherapy concerns the use of lytic viruses which selectively infect and kill cancer cells. Some oncolytic viruses are promising therapies as they display exquisite selection for replication in cancer cells and their self-li...

AI Technical Summary

Benefits of technology

[0121]In another aspect of the present invention a method of instructing a human patient with cancer by providing instructions to receive a combination treatment with a herpes simplex virus lacking functional ICP34.5 genes and an immune checkpoint inhibitor to extend survival of the patient, is provided.

[0492]Because most liver tumors are supplied by the hepatic artery, arterial embolization interrupts the blood supply to the tumor and delays tumor growth. The focused nature of the administration of active agents enables delivery of a high therapeutic dose to the tissue requiring treatment whilst reducing systemic exposure and therefore toxicity. Embolization of the vessel assists this process in that the active agent(s) is not washed out from the tumor bed and the supply of nutrients to the tumor is decreased thereby promoting tumor necrosis.

Problems solved by technology

The dosing regime involves numerous injections in different locations, which is generally disadvantageous for the patient.

It has also failed to statistically establish an overall survival benefit in any group of patients and shows limited evidence of a systemic effect, particularly in late stage and visceral disease.

Administration to human patients is exclusively by injection with notable patient reactions and the pre-clinical data indicates an unsuitability for systemic administration.

In many animal models, oncolytic viruses (including oncolytic herpes simplex viruses) work spectacularly well but repeating the results in human trials has proven challenging.

Brain tumors, deep-seated visceral tumors and multiple active metastases pose considerable barriers to successful intratumoral administration and attempts to treat such tumors are often accompanied by significant safety and technical issues, cost and resource requirements.

As reported in the Imlygic® data, the proposed use of intra-tumoral injection of an augmented oncolytic HSV expressing a cytokine (GM-CSF) to create a systemic therapy had limited success in advanced or visceral disease—even in melanoma where multiple intra-tumoral injections are relatively straight forward to carry out.

The optimal dose and route of administration, particularly for advanced, metastatic or visceral disease, remains a problem in the art of oncolytic viruses.

As has been seen with other oncolytic viruses, the effective application is not as straightforward as laboratory studies might have indicated.

Systemic administration of herpes simplex virus has been seen as problematic outside of model systems in the laboratory.

Despite the skill of the interventional radiologists, intra-tumoral injection had limited application to patients with such large tumor burden or advanced metastatic disease.

Intratumoral injection of herpes simplex viruses in clinical studies for the treatment of head and neck cancer has therefore led to disappointing results.

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