Effective Sensitizing Dose of a Gelled Immunomodulating Topical Composition

Abstract

The present invention relates to compositions and methods of treating warts and other human papilloma virus (HPV) skin infections. The present invention relates to compositions and methods of treating skin cancer.

Description

BACKGROUND OF THE INVENTION[0001]Human papilloma virus (HPV) is a small double-stranded DNA virus that colonizes various stratified epithelia like skin, oral and genital mucosa, and induces the formation of self-limiting benign tumors known as papillomas (warts) or condylomas. Most of these benign tumors naturally regress due to the influence of host immunological defenses. Some HPVs, however, have oncogenic potential and have been associated with certain types of cancers. See, Lorincz et al., Obstetrics & Gynecology, 79:328-337 (1992); Beaudenon et al., Nature, 321:246-249 (1986); and Holloway et al., Gynecol. Onc., 41:123-128 (1991).[0002]Infection with HPV is common. HPV can be transmitted sexually, and it is estimated that 20-80% of sexually active adults have been infected. While a majority of infections are asymptomatic, infection can lead to the development of genital warts (which have a prevalence of about 1-5% among adults) and cancer of the anogenital tract. Another type o...

AI Technical Summary

Benefits of technology

[0151]In the preferred treatment method, the subject is administered the immunological agent in an amount that is effective inhibiting proliferation of cancer cells in the subject. The dose administered and the dosing schedule will follow, for example, known or recommended doses for antibody agents currently in use for anti-tumor therapy, such as Rituximab, as indicated, for example, in the drug product insert or published clinical or animal-model data. One advantage of the present invention is that lower-than-normal doses of the immunological agent can be administered, if necessary, due to the compensating enhancement effect of the treatment regimen of the invention. Thus, a kit containing a dose of the immunological agent could optionally contain a product insert having one set of directions for using the agent in monotherapy, and another set of directions for using DPCP in a combination therapy to sensitize the subject. The set of instructions for the combination therapy could recommend a lower dose of the immunological agent, when used in combination with the treatment regimen of the invention, and / or a different dosing regimen for one or both agents, when used together, than would normally be recommended for the immunological agent when used alone.

[0152]The treatment regimen of the invention may be administered, before, during, or after administration of the immunological agent. Typically, the immunological agent and DPCP are administered in a common dosing regimen, and the two compounds themselves may be administered in a combined-drug composition. However, a dosing regimen in which the sensitizing and challenge dose of DPCP of the invention is administered before or after administering the immunological agent is also contemplated. For example, a subject under treatment with an immunological agent may be subsequently placed on a combined therapy that includes the treatment regimen of the invention.

[0153]Alternatively, the subject may be initially administered with the treatment regimen of the invention comprising a low sensitizing dose of DPCP and a challenge dose of DPCP followed by the administration of the immunological agent at a later time. In this type of treatment schedule, the low and high doses of DPCP serves, in part, to sensitize the cancer cells towards responding to the immunological agent.

[0154]The immunological agent may be administered by direct injection of a tumor or its vasculature. Alternatively, the tumor may be infused or perfused with the agents using any suitable delivery vehicle. The agents may be administered locally to an affected organ. Systemic administration may also be performed. Continuous administration may be applied where appropriate; for example, where a tumor is excised and the tumor bed is treated to eliminate residual disease. Delivery via syringe or catheterization is preferred. Such continuous perfusion may take place for a period from about 1-6 hours, to about 6-12 hours, to about 12-24 hours, to about 1-2 days, to about 1-2 weeks or longer following the initiation of treatment. Generally, the dose of the therapeutic composition via continuous perfusion will be equivalent to that given by a single or multiple injections, adjusted over a period of time during which the perfusion occurs.

[0155]The immunologic agent can be administered to a subject, such as a human patient, in a formulation and in an amount effective to achieve a clinically desirable result. For the treatment of cancer, desirable results include reduction in tumor mass (as determined by palpation or imaging; e.g., by radiography, radionucleotide scan, CAT scan, or MRI), reduction in the rate of tumor growth, reduction in the rate of metastasis formation (as determined e.g., by histochemical analysis of biopsy specimens), reduction in biochemical markers (including general markers such as ESR, and tumor specific markers such as serum PSA), and improvement in quality of life (as determined by clinical assessment, e.g., Karnofsky score), increased time to progression, disease-free survival and overall survival.

[0156]In another embodiment, the treatment regimen of the present invention can be combined with the use of Nitrogen mustard (mechlorethamine) in the treatment of cancer. Nitrogen Mustard is a chemotherapy drug that is normally given intravenously to treat the entire body. When mixed in an ointment, it is a useful treatment for lymphomas of the skin. In this regard, see for example, U.S. Patent Application Publication No. 20100041767 for compositions and methods of treating cancer comprising Nitrogen Mustard. The extensive disclosure provided in US20100041767 is incorporated by reference as if set forth in its entirety herein.EXPERIMENTAL EXAMPLES

Problems solved by technology

Because papillomaviruses tend to be host-specific and HPV has not been successfully grown in culture; the majority of the research with papilloma virus has been conducted with animal papillomaviruses.

However the management of in-transit disease remains extremely challenging.

However, high recurrence rates are a major obstacle to the complete eradication of cancerous cells.

It is believed that although the cancer cells in the malignant tumors can be removed surgically, cancerous cells that have invaded the surrounding tissue or lymph nodes frequently cause tumor recurrence.

One reason for frequent tumor recurrence may be that during the development of the primary cancer, complete removal of all the cancer cells by surgical procedures is extremely difficult.

Although irradiation, chemotherapy and appropriate hormone therapy all induce apoptosis to some extent in tumor cells, higher doses of the drugs or radiation may be required for suppressing the growth of cancer cells, which, in turn, can cause severe side effects on patients.