The Uab Research Foundation

Hudsonalpha Institute for Biotechnology

Albert F LoBuglio

Donald J Buchsbaum

Tong Zhou

Robert P Kimberly

William J Koopman

Kimihisa Ichikawa

Jun Ohsumi

Richard M Myers

Brian Scott Roberts

Kimberly Foreman

Theresa Strong

Robert M Conry

Jason Gertz

Andres Forero-Torres

Katherine E Varley

Jun Oshumi

The present disclosure provides for and relates to novel fusion proteins and polypeptides expressed by breast cancer and other cancer cells, and to compositions, materials and methods for detecting, characterizing and treating said breast and other cancers. In one embodiment, the fusion polypeptides are read-through fusion transcripts.

Method of treating breast cancer

Provided herein are methods of treating a subject with cancer comprising administering to the subject a death receptor agonist. Also provided herein are methods of screening a breast cancer cell for responsiveness to a DR5 agonist. Further provided herein are antibodies that selectively bind an N-terminal CARD of DDX3, a DDX3 lacking an N-terminal CARD, and an 80 kDa baculovirus TAP repeat (BIR).

Treating basal-like genotype cancers

Provided is a method of determining the level of resistance or sensitivity of cancer stem cells to a death receptor agonist. The method includes detecting the level of IAP in one or more DR5/DDX3/IAP complexes in or from the cancer stem cells. Also provided is a method of killing cancer stem cells in a subject and a method of reducing the risk of cancer recurrence in a subject.

Targeting cancer stem cells with DR5 agonists

An antibody of the invention interacts with human DR5 or with human DR4 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Methods and uses for the antibodies, optionally in combination with various therapeutic agents, are detailed, including treatment of apoptosis-related disease and treatment of dysregulated cell growth.

Combinations of antibodies selective for DR5 and other therapeutic agents

An antibody of the invention interacts with human DR5 or with human DR4 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Nucleic acid sequences and amino acid sequences of DR5 and DR4 antibodies have been elucidated and vectors and cells containing and expressing these sequences have been generated. Methods and uses for the antibodies are detailed including treatment of apoptosis-related disease and treatment of dysregulated cell growth.

Antibody selective for DR4 and uses thereof

Combinations of DR5 antibodies and other therapeutic agents

The present invention provides for isolated DNA and protein corresponding to novel melanoma tumor-associated antigens, antibodies directed towards the novel antigens of the present invention as well as methods of using the antigens for inhibiting the growth of a melanoma tumor and methods of screening compounds that inhibit the novel antigens of the present invention.

Melanoma antigens and methods of use

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Birmingham, AL, United States of America

Albert F LoBuglio