Duke University

Cornell Research Foundation Inc.

Johns Hopkins University

Schering Corporation

O. Michael Colvin

Henry S. Friedman

Darell D. Bigner

Henry S Friedman

Darell D Bigner

John Howard Sampson

Matthias Gromeier

Annick Desjardins

Owen W Griffith

O Michael Colvin

Allan H Friedman

Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. The mechanism of action is believed to involve both viral oncolysis as well as immune recruitment, both of which lead to necrosis in the area of the tumor. No adverse effects have been observed.

Oncolytic poliovirus for human tumors

Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. Sequential treatment with the virus construct followed by chemotherapy drugs increases the anti-tumor effect. Tumors of different types are susceptible to the combination treatment, including but not limited to melanoma, glioblastoma, renal cell carcinoma, prostate cancer, breast cancer, lung cancer, medulloblastoma, and colorectal cancer.

Sequential anti-cancer treatment

Methods are disclosed for treating cancer in a patient in need of such treating comprising administering temozolomide in an amount effective to achieve a clinical response wherein the temozolomide is administered in a microcrystalline suspension.

Methods of using temozolomide in the treatment of cancers

L-amino acid oxidase is utilized to reduce the plasma level of large neutral amino acids to allow the opportunity of increased large neutral amino acid drug transport across the blood brain barrier. Preferably anti L-amino acid oxidase antibody is administered intermediate to the L-amino acid oxidase and large neutral amino acid drug administrations to deplete L-amino acid oxidase activity once the L-amino acid oxidase has caused the large neutral amino acid drug transport improving level plasma reduction of large neutral amino acids thereby to reduce or eliminate degrading of large neutral amino acid drugs by L-amino acid oxidase. The large neutral amino acid drugs include levodopa, melphalan, L-DON, azaserine, acivicin, L-alanosine and 3-(phosphonomethyl)phenylalanines. For treatment of brain tumors, the drug administration is preferably preceded by the administration of a large neutral amino acid glutathione depleting agent, e.g., L-buthionine-SR-sulfoximine. L-Amino acid oxidase is also utilized to enhance the transport of large neutral amino acid glutathione depleting agent across the blood brain barrier as an adjunct to radiation therapy of brain tumors.

Enhancing delivery of large neutral amino acid drugs

L-amino acid oxidase is utilized to reduce plasma level of large neutral amino acids to allow the opportunity of increased melphalan transport into tumors and melphalan is administered when the plasma level of L-amino acid oxidase is sufficiently low so the gain from increased transport outweighs the loss from L-amino acid oxidase-mediated metabolism of melphalan. Preferably anti L-amino acid oxidase antibody is administered intermediate the L-amino acid oxidase and melphalan administrations to deplete L-amino acid oxidase activity once the L-amino acid oxidase has caused the melphalan transport improving plasma level reduction of large neutral amino acids thereby to reduce or eliminate degrading of melphalan by L-amino acid oxidase.

Enhancing the anti-tumor effect of melphalan by prior administration of

L-amino acid oxidase is utilized to reduce plasma level of large neutral amino acids to allow the opportunity of increased melphalan transport into tumors and melphalan is administered when the plasma level of L-amino acid oxidase is sufficiently low so the gain from increased transport outweighs the loss from L-amino acid oxidase-mediated metabolism of melphalan.

Enhancing the anti-tumor effect of melphalan with L-amino acid oxidase

A method of treating human tumors is provided in which tumors are regionally treated with a cytolytic, pre-activated, bifunctional alkylating agent, namely 4-hydroperoxycyclophosphamide. The treatment is effective against a variety of tumor types within the central nervous systems.

Growing community of inventors

Durham, NC, United States of America

Henry S Friedman