The Uab Research Foundation

Murray A Stackhouse

David T Curiel

Donald J Buchsbaum

David Raben

Lee C Pederson

Mohammad B Khazaeli

Mohammad B Khazaell

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.

Molecular chemotherapy enhancement of radiotherapy

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 a method to achieve radioisotopic localization at tumor sites, i.e., a method of enhancing radiolabeled ligand localization to a tumor in an individual in need of such treatment, comprising the steps of: transducing said tumor with a gene encoding a membrane expressed protein unique to said tumor; and administering to said individual a radiolabeled ligand which specifically binds to said protein. The use of gene therapy technology to induce expression of high affinity membrane molecules/receptors can enhance the specificity of radioisotope localization while the use of radioactive isotopes with the ability to deliver radiation damage across several cell diameters will compensate for less than perfect transduction efficiency.

Genetic induction of receptors for targeted radiotherapy

The present invention provides a method to achieve radioisotopic localization at tumor sites, i.e., a method of enhancing radiolabeled ligand localization to a tumor in an individual in need of such treatment, comprising the steps of: transducing the tumor with a gene encoding a membrane expressed protein unique to the tumor; and administering to said individual a radiolabeled ligand which specifically binds to the protein. The use of gene therapy technology to induce expression of high affinity membrane molecules/receptors can enhance the specificity of radioisotope localization while the use of radioactive isotopes with the ability to deliver radiation damage across several cell diameters will compensate for less than perfect transduction efficiency.

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Birmingham, AL, United States of America

Murray A Stackhouse