Methods and compositions for cancer therapy using a novel adenovirus

Abstract

The invention comprises a novel virus that can kill mammalian cancer cells efficiently. The virus produces a novel protein that converts two non-toxic prodrugs into potent chemotherapeutic agents. These chemotherapeutic agents are produced locally and help the virus kill the cancer cells as well as sensitize them to radiation. In preclinical studies, the virus has proven effective at killing a variety of mammalian cancer cells either alone or when combined with prodrug therapy and / or radiation therapy. The invention may provide a safe and effective treatment for human cancer.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation-in-part of presently pending U.S. patent application Ser. No. 10 / 888,492, filed Jul. 9, 2004, entitled “Methods And Compositions For Cancer Therapy Using a Novel Adenovirus,” which claims priority to U.S. provisional applications 60 / 486,219, filed Jul. 9, 2003, both of which are hereby fully incorporated herein by reference.FIELD OF THE INVENTION[0002]Generally, the present invention relates to a cancer therapy. More specifically, the present invention relates to an adenovirus-based cancer therapy.BACKGROUND[0003]Despite advances in both diagnosis and therapy, the annual number of cancer related deaths has not decreased during the past 60 years. Although conventional cancer therapies (surgery, radiotherapy, chemotherapy) produce a high rate of cure for patients with early stage disease, many cancers recur and the majority of patients with advanced cancer eventually succumb to the disease. The limitations...

AI Technical Summary

Benefits of technology

[0011]The present invention comprises novel, improved methods and compositions for cancer therapy which comprise a novel virus that can kill mammalian cancer cells efficiently. The virus produces a novel protein that converts non-toxic prodrugs into potent chemotherapeutic agents. These chemotherapeutic agents are produced locally and help the virus kill the cancer cells as well as sensitize them to radiation. In preclinical studies, the virus has proven effective at killing a variety of human cancer cells either alone or when combined with prodrug therapy and / or radiation therapy.

[0012]The invention comprises a novel, “second-generation” adenovirus (designated “Ad5-yCD / mutTKSR39rep-ADP”) with at least two significant improvements relative to the previously disclosed prototype Ad5-CD / TKrep virus. Ad5-yCD / mutTKSR39rep-ADP contains an improved yCD / mutTKSR39 fusion gene whose product is more, efficient at converting the 5-FC and GCV prodrugs into their active chemotherapeutic agents. Moreover, Ad5-yCD / mutTKSR39rep-ADP expresses the Ad5 ADP protein, which significantly increases the oncolytic activity of replication-competent adenoviruses. Relative to the prototype Ad5-CDITKrep virus, Ad5-yCD / mutTKSR39rep-ADP has demonstrated greater viral oncolytic and chemotherapeutic activity in preclinical cancer models. The data suggest that the Ad5-yCD / mutTKSR39rep-ADP virus comprising the present invention will exhibit low toxicity and significant anti-tumor activity clinically when combined with 5-FC and GCV prodrug therapy and radiation therapy.

Problems solved by technology

The limitations of conventional cancer therapies do not derive from their inability to ablate tumor, but rather from limits on their ability to do so without excessively damaging the patient.

Surgical methods, however, can be limited due, for example, to the location of a tumor or to dissemination of metastatic tumor cells.

Radiotherapy also can be limited by other factors that limit the dose that can be administered.

Tumors that are relatively radioresistant will not be cured at such a dose.

Unfortunately, the therapeutic usefulness of radiation therapy can be limited where the tumor cells are relatively radioresistant, since the dose is limited by the tolerance of normal tissue in the radiation field.

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