Adaptive Phased Array Microwave Heating to Eradicate Tumors
Summary:
An SDIO-funded adaptive phased-array (APA) microwave focusing technique, originally developed for missile radar applications, is being used in clinical trials for the treatment of breast cancer.
Technology Description:
Adaptive phased array technology enables the user to focus, and to cancel or “null”, microwave radiation selectively in a given space, using antennas and software.
MDA Origins:
MIT Lincoln Laboratory designed and developed an APA microwave antenna in an electromagnetically quiet, non-reflecting chamber to simulate space-based radar transmission. The APA algorithms are similar to those used for adaptive optics. The effort was funded by SDIO, and the research was performed at MIT Lincoln Laboratory, a Federally Funded Research and Development Center.
Spinoff Applications:
Celsion Corporation, with Dr. Cheung at the helm, developed a successful thermal therapy platform for benign prostatic hyperplasia based on application of radiofrequency-generated heat. Celsion will continue to target breast cancer, prostate cancer, and liver cancer in its drug development program, while Dr. Cheung’s APA technology venture will initially target breast cancer under the auspices of his new company, Celsion Canada.
Commercialization:
Celsion (formerly Cheung Laboratories, Inc.), licensed MIT’s APA microwave technology and incorporated it into a device, the Microfocus 1000TM, for the purposes of eradicating tumors by deep, focused microwave heating. This device received a pre-market approval from the Food and Drug Administration in 1997. The principal advantage of APA-based heating is that the clinician can focus microwave energy on tumors and avoid unwanted heating in normal tissue, as APA technology can “null” or cancel out microwave radiation in normal, healthy tissue. Thermal ablation of tumors is not a new method, but only surface or near-surface tumors can be treated with currently available devices. The APA approach is unique in being able to heat deep inside the body without heating the skin or surrounding healthy tissue. Celsion went on to develop other heating platforms, using radiofrequency instead of microwaves, but has always kept APA on the back burner while it pursued development of thermal therapies for prostatic hyperplasia and liver cancer.
In addition to eventual adaptation of APA, Celsion had also hoped to develop a liposome-based drug delivery system in conjunction with the heating device. The company has indeed accomplished this objective, but also in conjunction with a radiofrequency heating technique instead of APA. By encapsulating a toxic chemotherapeutic agent such as doxorubicin (adriamycin) in a liposome (a simple fatty sphere that is commonly used in cosmetics and pharmaceuticals), the drug can travel inertly through the bloodstream to the tumor site, to be released by thermal activation. The heat melts the membrane of the liposome and releases the drug. In this way, the drug can both act systemically to treat micrometastases, and the drug’s activity at the primary tumor site can be concentrated at the site at high levels. Celsion terms this system ThermoDox, for thermal activation of doxorubicin, and has been conducting phase I clinical trials in liver cancer patients.
Throughout the development of these related thermal technologies, Dr. Cheung has remained devoted to the concept of using APA in the treatment of breast cancer, both alone and in combination with chemotherapy. Two studies have been published detailing the safety and efficacy of APA microwave heating of breast tumors, both appearing in the Annals of Surgical Oncology [9:326-332 (2002), 11:139-146 (2004)]. These studies verified the basic utility of APA microwave heating and concluded that the degree of tumor necrosis (tissue death) was related to the thermal dose and caused minimal damage to healthy tissues around the tumor. Dr. Alan Fenn, developer of the APA technology, is a co-author of both papers.
Intellectual Property
In early 2006, Celsion Corporation announced that it would be moving in the direction of refining its drug application focus. At that time, company founder Dr. Augustine Cheung resigned from Celsion’s Board of Directors and from his position as Chief Scientific Officer, and acquired all assets related to the APA heating technology for the purpose of further developing the technology to treat breast cancer. Trials with a non-APA heating device combined with chemotherapeutic agents have been conducted in both animals and humans, with significant results, and Dr. Cheung is preparing to take the next step with similar trials that employ a similar drug protocol, but with APA heating. The current strategy is to use APA in a standard-of-care trial that will combine APA thermotherapy with established chemotherapy agents, doxorubicin and other drugs, in a neoadjuvant setting for locally advanced breast cancer. In this setting, the drugs are administered before surgery to reduce the volume of the tumor, in an effort to avoid mastectomy or to simply reduce the amount of breast tissue removed. The drug delivery will not be liposomal, but in other respects these trials will be quite similar to those Celsion has completed in the past, and the chief difference will be the APA heating technology. Clinical trials are planned for 2006 at centers in the U.S., Canada, and possibly China; centers in the U.S. that are currently lined up include the University of Oklahoma Health Sciences Center (Oklahoma City, OK), Harbor-UCLA Medical Center (Torrance, CA), and St. Joseph Comprehensive Breast Center (Orange, CA). .
Company Profile:
Over the years, Celsion has developed a solid reputation in the application of heat in both cancerous and noncancerous conditions, such as in the treatment of benign prostatic hyperplasia (BPH). In 2004, Celsion granted Boston Scientific Corporation exclusive marketing rights to the Prolieve System (which uses radio frequency waves, not the APA technology), with an option to purchase assets and technology relating to the system, a deal that is potentially worth $60 million.
The new focus of APA technology will be undertaken via Dr. Cheung and his new company, Celsion Canada.
Contact Information:
Mr. John Mon
Celsion Corporation
10220-L Old Columbia Road
Columbia, MD 21046-1705
410-290-5734 ext: 3
fax: 410-290-7255
email: jmon@celsioncanada.com
web: www.celsion.com
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