Combination therapy using active immunotherapy

Abstract

The present invention relates to methods of treating cancer in a mammal comprising administering to the mammal a combination therapy comprising a vaccine and a multi-kinase inhibitor, wherein the vaccine comprises an isolated tumor associated peptide having the ability to bind to a molecule of the human major histocompatibility complex (MHC) class-I or class-II. Preferably the multi-kinase inhibitor is sunitinib malate and / or sorafenib tosylate or a pharmaceutically acceptable salt thereof.

Description

RELATED APPLICATIONS[0001]This application is based on, and claims priority to, U.S. provisional application 60 / 908,012, which was filed on Mar. 26, 2007, and the entire contents of the provisional application are incorporated by reference in its entirety.BACKGROUND OF THE INVENTION[0002]Although there have been great improvements in the diagnosis and treatment of cancer, many people die from cancer each year, and their deaths are typically due to metastases and cancers that are resistant to conventional therapies.[0003]Most drug-mediated cancer therapies rely on chemotherapeutical agents, i.e. cytotoxic agents, selective for dividing cells. These agents are usually administered at or near maximum tolerated doses resulting in frequent dramatic toxicities that compromise the quality of life and have a severe effect on the immune response. However, such drugs almost inevitably do not kill all of the cancer cells in the patient since some of them acquire a resistance against the partic...

AI Technical Summary

Benefits of technology

The present invention provides a method of treating neoplastic disorders in mammals, including humans, by administering an active immunotherapy and at least one additional therapeutic agent. The active immunotherapy may include a vaccine or immunogenic peptides, while the therapeutic agent may be a multi-kinase inhibitor or a tyrosine kinase inhibitor, such as sunitinib malate or sorafenib tosylate. The combination therapy may be used as a sole treatment, an adjuvant, a neoadjuvant, or a palliative therapy. The routes of administration may be different or the same. The invention is particularly useful for treating cancer, such as renal cancer, and the vaccine may include peptides that bind to MHC class-I or class-II.

Problems solved by technology

Although there have been great improvements in the diagnosis and treatment of cancer, many people die from cancer each year, and their deaths are typically due to metastases and cancers that are resistant to conventional therapies.

These agents are usually administered at or near maximum tolerated doses resulting in frequent dramatic toxicities that compromise the quality of life and have a severe effect on the immune response.

However, such drugs almost inevitably do not kill all of the cancer cells in the patient since some of them acquire a resistance against the particular drug.

However, no combinations with active immunotherapy are disclosed.

However, no combination treatment with therapeutical anti-neoplastic doses of a chemotherapeutic was disclosed.

Virtually all chemotherapeutics, including kinase inhibitors cause depression of the immune system when used in therapeutical doses, often by paralysing the bone marrow and leading to a decrease of white blood cells, red blood cells and platelets.

Depending on their target, some monoclonal antibodies used in cancer therapy also have a detrimental effect on the immune system.

Thus, it was surprising to find, that small molecules, kinase inhibitors and antibodies that lead to a suppressed immune system do not prevent the desired immune response when used in combination with active immunotherapy.

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