University of South Florida

Old Dominion University Research Foundation

Old Dominion University

Genetronics, Inc.

Other

Yale University

Vanderbilt University

Eastern Virginia Medical School

Richard M Heller

Mark Jeffrey Jaroszeski

Richard A Gilbert

Karl H Schoenbach

Loree C Heller

Melinda Lee Lucas

Gunter A Hofmann

Kenneth E Ugen

Mark Jeffery Jaroszeski

Paul R Sanberg

Shu Xiao

Andrew M Hoff

Don F Cameron

Yasuhiko Hayakawa

James Thomas Camp

Jose I Rey

Stephen P Beebe

Amy Donate

Said M Sebti

Andrew D Hamilton

Richard Jove

Hua Yu

Cesario V Borlongan

William S Dalton

Stephen J Beebe

Thomas F Lachner

Drew Hoff

S B Dev

Chen Yeong-Jer

William Marshall

Jennifer Langham

Sukhendo B Dev

Dan Roman

Raymond T Matyas

Sergio Corona

A method of treating cancerous tumors is presented herein. The method includes injecting an effective dose of a plasmid encoded for IL-12, B7-1 or IL-15 into a cancerous tumor and subsequently administering at least one high voltage, short duration pulse to the tumor. The electroporation pulses may be administered at least 700V/cm for a duration of less than 1 millisecond. The intratumor treatments with electroporation may be administered in at least a two-treatment protocol with the time between treatments being about 7 days. The intratumor treatments with electroporation may be administered in a three-treatment protocol with a time of four days between the first and second treatments and a time of three days between the second and third treatments. It was found that the intratumor treatments using electroporation not only resulted in tumor regression but also induced an immune memory response which prevented the formation of new tumors.

Method for the treatment of malignancies

A method and system for delivering a molecule to a specific area of a tissue by controlling temperature and impedance is presented. The method is generally comprised of applying heat to a biological structure, such as cells or tissues, to heat the biological structure to a preset temperature after which at least one electroporation pulse is administered to the biological structure. Impedance is measured as a feedback control mechanism after each pulse and pulse parameters are adjusted accordingly until desired impedance is reached. The system generally comprises an electroporation system capable of generating at least one pulse, measuring impedance and measuring temperature. The method may be used to deliver a molecule such as a vaccine or therapeutic to a biological structure, such as for prevention or treatment of SARS-CoV-2 infection.

Targeted delivery of molecules using impedance-based monitoring at elevated temperatures

A method and system for delivering a molecule to a specific area of a tissue by controlling temperature and impedance is presented. The method is generally comprised of applying heat to a biological structure, such as cells or tissues, to heat the biological structure to a preset temperature after which at least one electroporation pulse is administered to the biological structure. Impedance is measured as a feedback control mechanism after each pulse and pulse parameters are adjusted accordingly until desired impedance is reached. The system generally comprises an electroporation system capable of generating at least one pulse, measuring impedance and measuring temperature.

Targeted delivery of molecules using impedence-based monitoring at elevated temperatures

Systems and methods for treating or manipulating biological tissues are provided. In the systems and methods, a biological tissue is placed in contact with an array of electrodes. Electrical pulses are then applied between a bias voltage bus and a reference voltage bus of a distributor having switching elements associated with each of the electrodes. The switching elements provide a first contact position for coupling electrodes to bias voltage bus, a second contact position for coupling electrodes to the reference voltage bus, and a third contact position for isolating electrodes from the high and reference voltage buses. The switching elements are operated over various time intervals to provide the first contact position for first electrodes, a second contact position for second electrodes adjacent to the first electrodes, and a third contact position for a remainder of the electrodes adjacent to the first and second electrodes.

Multi-electrode electrical pulse delivery system for treatment of biological tissues

A method of treating cancerous tumors is presented herein. The method includes injecting an effective dose of a plasmid encoded for IL-12, B7-1 or IL-15 into a cancerous tumor and subsequently administering at least one high voltage, short duration pulse to the tumor. The electroporation pulses may be administered at al least 700 V/cm for a duration of less than 1 millisecond. The intratumor treatments with electroporation may be administered in at least a two-treatment protocol with the time between treatments being about 7 days. The intratumor treatments with electroporation may be administered in a three-treatment protocol with a time of four days between the first and second treatments and a time of three days between the second and third treatments. It was found that the intratumor treatments using electroporation not only resulted in tumor regression but also induced an immune memory response which prevented the formation of new tumors.

Catheter devices can include an elongate housing extending along a major axis, the elongate housing comprising a first end an opening. The catheter devices can also include an electrode assembly disposed in the elongate housing and including deformable electrodes with respective electrode distal ends, where the electrode distal ends each consist of respective member portions and respective tip portions. The electrode assembly is slidably movable within the housing along the major axis to allow the electrode distal end portions to transition between a first retracted position and a second extended position. The catheter device is configured such that an average distance between the tip portions in the second position is configured to be greater than an average distance between the tip portions in the first position the tip portions are positioned substantially in a same plane when the electrode assembly is in the second position.

Expandable catheter devices electrode array

Systems and methods for treatment of a biological tissues including target tissues and other tissues. The method includes elevating a temperature of the target tissues above a physiological temperature of the biological tissues to treatment temperature, and generating an electric field extending through at least a portion of the target tissues using a pre-defined sequence of short voltage pulses applied between at least two electrodes. In the method, the treatment temperature is maintained during the generating. Further, the pre-defined sequence is selected such that a magnitude of the electric field generated is sufficient to induce electromanipulation in the portion of the target tissues without substantially elevating of the temperature of the portion of the target tissues above the treatment temperature.

Electromanipulation of cells and other biological tissues by pulsed electric fields at elevated temperatures

A method of treating cancerous tumors is presented herein. The method includes injecting an effective dose of a plasmid encoded for IL-12, B7-1 or IL-15 into a cancerous tumor and subsequently administering at least one high voltage, short duration pulse to the tumor. The electroporation pulses may be administered at at least 700V/cm for a duration of less than 1 millisecond. The intratumor treatments with electroporation may be administered in at least a two-treatment protocol with the time between treatments being about 7 days. The intratumor treatments with electroporation may be administered in a three-treatment protocol with a time of four days between the first and second treatments and a time of three days between the second and third treatments. It was found that the intratumor treatments using electroporation not only resulted in tumor regression but also induced an immune memory response which prevented the formation of new tumors.

Systems and methods for treatment of a biological tissues comprising target tissues and other tissues. The method includes elevating a temperature of the target tissues above a physiological temperature of the biological tissues to treatment temperature, and generating an electric field extending through at least a portion of the target tissues using a pre-defined sequence of short voltage pulses applied between at least two electrodes. In the method, the treatment temperature is maintained during the generating. Further, the pre-defined sequence is selected such that a magnitude of the electric field generated is sufficient to induce electromanipulation in the portion of the target tissues without substantially elevating of the temperature of the portion of the target tissues above the treatment temperature.

The present invention provides a system and method of directing, focusing, or concentrating electrical charges within a defined electric field so that these charges can be used to exert forces on cells and tissues in vivo and/or cell cultures in vitro. The present invention reduces and/or eliminates the damage at a target site that would normally be caused by an electrode that acts as a current source or sink to accomplish the same task.

Passive electric field focus system for in vivo and in vitro applications

Signal Transducer and Activator of Transcription (STAT) proteins have a fundamental role cell signaling, and are activated by a large number of cytokines and growth factors. One member of the STAT family, STAT3, has a critical role in oncogenesis. The present invention relates generally to disruption of the pathway of STAT3 signaling in the treatment of human cancer. STAT3 activation is shown to be present in diverse tumor cell lines and tumors, to promote oncogenesis, to inhibit apoptosis, and to reduce sensitivity to chemotherapeutic agents. Inhibition of STAT3 signaling induces apoptosis specifically in tumor cell lines, and increases sensitivity to chemotherapeutic agents. The invention relates more particularly to methods, compositions, means of administering such compositions, and means for identifying such compositions for the inhibition of STAT3 intracellular signaling in the treatment of human cancers.

Inhibition of STAT3 signal transduction for human cancer therapy

Growing community of inventors

Nashville, TN, United States of America

Richard M Heller