The UAB Research Foundation (The University of Alabama at Birmingham)

Other

University of Minnesota

Hudsonalpha Institute for Biotechnology

Beijing Cotimes Biotech Co. Ltd.

Donald J Buchsbaum

Tong Zhou

Albert F LoBuglio

David T Curiel

Murray A Stackhouse

Robert P Kimberly

William J Koopman

Kimihisa Ichikawa

Jun Ohsumi

Daniel A Vallera

G Yancey Gillespie

C Ryan Miller

David Raben

Albert F Lobuglio

Bruce Robert Blazar

Richard M Myers

Enyun Shen

Ahmad Safavy

Brian Scott Roberts

Robert Garver, Jr

Xian Chen

Robert J Garyer, Jr

Andres Forero-Torres

Katherine E Varley

Jason Gertz

Mohammad B Khazaell

Mohammad B Khazaeli

Mohammad Bagher Kazaeli

Lee C Pederson

Kimberly Foreman

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 herein are antibodies specific for HER3. Also provided are methods of treating cancer in a subject comprising administering an effective amount of the antibodies described herein to the subject.

HER3 antibodies and uses thereof

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 a new approach for cancer treatment by utilizing gene therapy combined with radiation therapy to enhance cytotoxicity in malignant cells. Specifically, the present invention demonstrates that molecular chemotherapy with the cytosine deaminase gene and 5-fluorocytosine is an effective radiosensitizing strategy which may lead to substantial improvement in tumor control, with less normal tissue toxicity than conventional systemic administration of 5-fluorouracil, that would translate into improved cure rates and better survival. A noninvasive method is described for continuous in vivo monitoring of 5-fluorouracil production via magnetic resonance spectroscopy An adenovirus encoding cytosine deaminase gene which selectively replicates in tumor cells with a defective p53 pathway was constructed. Also provided is an adenovirus which encodes a fusion protein of cytosine deaminase and uracil phosphoribosyltransferase.

Molecular chemotherapy enhancement of radiotherapy

The present invention provides a new approach for cancer treatment by utilizing gene therapy combined with radiation therapy to enhance cytotoxicity in malignant cells. Specifically, the present invention demonstrates that molecular chemotherapy with the cytosine deaminase gene and 5-fluorocytosine is an effective radiosensitizing strategy which may lead to substantial improvement in tumor control, with less normal tissue toxicity than conventional systemic administration of 5-fluorouracil, that would translate into improved cure rates and better survival. Also provided is a noninvasive method for continuous in vivo monitoring of 5-fluorouracil production via magnetic resonance spectroscopy.

The present invention provides a new approach for cancer treatment by utilizing gene therapy combined with radiation therapy to enhance cytotoxicity in malignant cells. Specifically, the present invention demonstrates that molecular chemotherapy with the cytosine deaminase gene and 5-fluorocytosine is an effective radiosensitizing strategy which may lead to substantial improvement in tumor control, with less normal tissue toxicity than conventional systemic administration of 5-fluorouracil, that would translate into improved cure rates and better survival. A noninvasive method is described for continuous in vivo monitoring of 5-fluorouracil production via magnetic resonance spectroscopy. An adenovirus encoding cytosine deaminase gene which selectively replicates in tumor cells with a defective p53 pathway was constructed. Also provided is an adenovirus which encodes a fusion protein of cytosine deaminase and uracil phosphoribosyltransferase.

The present invention provides a method of enhancing the chemosensitivity and radiosensitivity of a neoplastic cell expressing an oncoprotein that stimulates proliferation of the cell, comprising introducing into the cell a nucleic acid molecule encoding an antibody homologue, wherein the antibody homologue is expressed intracellularly and binds to the oncoprotein intracellularly in the endoplasmic reticulum of the cell. The present invention is also directed to a method for enhancing the inhibition of proliferation of a neoplastic cell expressing an oncoprotein that stimulates proliferation of the cell, comprising the steps of: introducing into the cell a nucleic acid molecule encoding an antibody homologue, wherein the antibody homologue is expressed intracellularly and binds to the protein intracellularly; and contacting said cell with an anti-neoplastic agent.

Enhancement of tumor cell chemosensitivity and radiosensitivity using single chain secretory antibodies

Enhancement of tumor cell radiosensitivity using single chain

The present invention provides the synthesis and purification of a new class of compounds known as radiolabeled fusion toxins (RFT), in which both toxin and radionuclide tags are contained on the same growth factor, for example, murine granulocyte macrophage colony stimulating factor, mGM-CSF, epidermal growth factor, or murine interleukin-4, mIL-4.

Radiolabeled fusion toxins for cancer therapy

Growing community of inventors

Birmingham, AL, United States of America

Donald J Buchsbaum