University of Pennsylvania

Wake Forest University

Fox Chase Cancer Center

University of the Sciences in Philadelphia

Gary D Kao

Stephen M Hahn

Jay F Dorsey

Emigdio Reyes

Roger J Pomerantz

Steven J Kridel

Anna Marie Skalka

Adeboye Adejare

Constantinos Koumenis

Brian E Lally

Rene Daniel

Giuseppe Nunnari

A method useful for identifying and isolating live circulating tumor cells is described. The method utilizes an adenoviral vector comprising a replication-competent adenovirus in which the E1 gene region is expressed under the control of a telomerase-specific promoter and further comprises a second expression cassette containing a marker protein, optionally fused to a detectable cell surface marker to permit detection of circulating tumor cells lacking cell surface markers. The method involves combining ex vivo a test sample from a patient suspected of having circulating tumor cells, an adenoviral probe system, and culture media for the cells. The test sample is incubated with the adenoviral system for a sufficient time to permit expression of the reporter protein. The marker gene expression can thereafter be quantitated and the marker-expressing cells may optionally be collected for further analysis.

Compositions and methods for isolation of circulating tumor cells (CTC)

A repeatable method for detecting circulating tumor cells in vitro is provided. The method involves combining a test sample from a patient suspected of having circulating tumor cells, and a non-lytic adenoviral system, and culture media for the cells. The adenoviral system utilizes (i) a first replication-defective adenoviral particle in which an expression cassette is packaged, said expression cassette comprising an adenoviral 5' and 3&#x2032; ITRs and a tumor-specific promoter; and (ii) a coding sequence for a reporter protein which is expressed in the presence of circulating tumor cells, and an adenoviral 3&#x2032; ITR. The test sample and the non-lytic adenoviral system are incubated for a sufficient time to permit expression of the reporter protein, and measuring reporter protein expression in the test samples, whereby presence of reporter expression indicates the presence of circulating tumor cells in the sample. Because the system is non-lytic, the testing can be repeated on the cells which remain viable in culture. Also provided is a method for enriching test samples having circulating tumor cells and a microfluidics device suitable for CTC-specification identification and enumeration.

Compositions, methods and microfluidics device for telomerase based in vitro diagnostic assays for detecting circulating tumor cells (CTC)

A repeatable method for detecting circulating tumor cells in vitro is provided. The method involves combining a test sample from a patient suspected of having circulating tumor cells, and a non-lytic adenoviral system, and culture media for the cells. The adenoviral system utilizes (i) a first replication-defective adenoviral particle in which an expression cassette is packaged, said expression cassette comprising an adenoviral 5' and 3&#x2032; ITRs and a tumor-specific promoter; and (ii) a coding sequence for a reporter protein which is expressed in the presence of circulating tumor cells, and an adenoviral 3&#x2032; ITR. The test sample and the non-lytic adenoviral system are incubated for a sufficient time to permit expression of the reporter protein, and measuring reporter protein expression in the test samples, whereby presence of reporter expression indicates the presence of circulating tumor cells in the sample.

The present invention comprises compounds, compositions and methods of use for sensitizing cancer cells, tumors, neoplasms, and malignancies to the effects of ionizing radiation used in the treatment of cancer. The invention further comprises a method of identifying novel radiosensitizing compounds.

Compounds for treatment of malignant tumors

Cellular targets for anti-retroviral drug development are disclosed. The cellular targets comprise ATR kinase and its relevant substrates, based on the identification of the ATR kinase as required for the final step of retroviral DNA integration. Assays for identifying modulators of retroviral integration via the ATR kinase pathway are disclosed, as well as modulators identified by such assays. Pharmaceutical preparations and methods of their use in treating retroviral infection are also disclosed.

Cellular targets for treatment of retroviral infection

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Wynnewood, PA, United States of America

Gary D Kao