• 9/9/2005
  • Atlanta, GA
  • Russell A. Jackson
  • Nanobiotech News Vol. 3, No. 26, July 13, 2005

Researchers in Germany are set to launch in 2007 a cancer treatment using targeted nanoparticles, heat and electromagnetism. The therapy, its developers say, is painless and side effect free. The MFH 300F therapy system, developed by Berlin’s MagForce Nanotechnologies GmbH, “generates an extremely homogeneous magnetic field, which changes its polarity 100,000 times a second,” explains Andreas Jordan, CEO. “The MagForce iron oxide-containing nanoparticles follow those changes in magnetization. Due to the high field homogeneity, all the particles take the same amount of energy out of the magnetic field, thus generating the same amount of heat. That’s crucial to obtaining a lasting therapeutic effect on the overall tumor volume.” MagForce, through its Center of Biomedical Nanotechnology, uses that heat for cancer therapy at high temperatures or to increase the efficacy of drugs and radiation at lower temperatures. The therapy system — dubbed MFH300F — is safe for the patient and medical personnel, he adds.

To date, researchers have observed some 300 treatments on 50 or so patients with “no pain and no burns or other severe side effects.” MFH stands for “magnetic fluid hyperthermia.”

The MagForce nanoparticles consist of an iron oxide core of 15 nm with at least one shell made of proprietary organic-anorganic compounds. The coating is adaptable to different tumor types, and the shell structure leads to uptake of the particles into tumor cells but not into normal cells of the same type of tissue. “For therapeutic success,” Jordan explains, “nanoparticle infiltration into the tumor only is necessary. Intracellular uptake is an add-on feature that’s relevant in terms of repeatability and specificity of the treatment, but it’s not a pre-condition for therapeutic effectiveness.”

Now, he adds, the company’s products must be injected directly into the tumor using conventional methods. “In about five years, targeting of our particles will allow intravascular administration, and no further intratumoral injection will be necessary,” he says.

With brain tumors, he notes, “we currently use a stereotactically navigational-guided application. With prostate carcinomas, we use sonographic control. With all other tumors, we use CT control to guide the particles into the tumors.”

After the nanoparticles have been taken up, they generate heat within the cell, which leads to cell necrosis and apoptosis. “The tumor cells are not able to get rid of them,” Jordan says. “That means that they are labeled for diagnostic and for therapeutic interventions. All conventional techniques deliver heat according to imaging information, which defines the ‘target volume.’ But burning out the target volume with excessive heat and/or radiation does not lead to curative results because the remaining tumors cells at the edges will re-grow. Through uptake of the particles, the tumor cells obtain some kind of an antenna for magnetic field energy, so that each tumor cell is in fact recognized and destroyed on a cellular level.”

Only nanoparticles, with their corresponding coating, he adds, are detected late by the immune system, so that they reach their target; can be absorbed by tumor cells in great quantities; and form a homogenous liquid of low viscosity in water. The system represents “a breakthrough in thermotherapy,” he says, because none of the other methods on the market can make these claims, which MagForce therapy, he says, has already demonstrated in clinical studies:
• It’s tumor-specific and leaves normal tissue unharmed.
• It’s minimally invasive, except for the nanoparticle application, which is done with a needle that’s comparable to an insulin syringe.
•It can be repeated as often as necessary, even in the case of recurrent tumor growth.
• It’s “precisely planned” on a millimeter scale and can be adjusted precisely to the desired temperature within the tumor.
•The nanoparticle application is non-toxic and non-radioactive and does not induce any damage to normal tissue.
•It can be combined with conventional therapies, like surgical intervention, irradiation and chemotherapy. Indeed, MagForce says, thermal treatment enhances the overall efficacy of multimodal treatments.
•And hyperthermia and thermoablation can be combined within the same patient.

Studies started in 1993

The clinical studies that back up those claims, Jordan points out, date back to 1993, when the International Journal of Hyperthermia published “Inductive heating of ferrimagnetic particles and magnetic fluids: physical evaluation of their potential for hyperthermia.” Since then, numerous studies have been published or prepared for publication.

Additionally, Jordan reports, the company has six more studies in various stages of completion. One, a feasibility study called “Local increase of efficacy of the standard therapy of Glioblastoma Multiforme or multilocular brain metastases by magnetic fluid hyperthermia,” wrapped last July and has just been submitted for publication.

Commercialization of the thermo-therapy has been started already, even before European Union regulatory approval, “because European customers can buy MagForce products to use them in clinical studies.” A system has already been installed at Charité Hospital, Berlin, at which more than 10 clinical disciplines are involved in clinical studies with MagForce products. Further installations at several sites in Germany, Switzerland and Austria are under negotiation. Full market entry is expected in 2007.

The MFH300F therapy devices — and the Mag- Force nanoparticles and all accessories — are ready for delivery in the EU now if clinical studies are conducted, Jordan adds. “Approved MagForce products outside clinical studies will be available in the EU not before 2007,” he says. “Series production of all components is in place, and availability of MagForce products outside the EU will depend on future strategic partners — and on Food and Drug Administration approval.”

The company already has the non-regulatory approval of a powerful thought leader in the nanobiotech sector. It received a Frost & Sullivan 2005 Technology Innovation Award for the European nanotechnology industry. Citing its “development of a path-breaking nano-based cancer therapy that enables the precise targeting of cancer cells in almost any part in the body with millimeter precision,” the London-based F&S also lauded Mag- Force’s “innovative technologies for glioblastoma — an aggressive form of brain tumor — and prostate carcinoma.”

MagForce began in 1998 as MFH Hyperthermiesysteme GmbH, which made the MFH300F product and the temperature measurement devices. In 2000, MagForce Applications GmbH was founded; it contributed nanoparticle development. In 2002, Jordan founded a holding company to market all products under the same label, and in 2004 all three were fused into MagForce Nanotechnologies GmbH.

“In the very near future,” he adds, “we will change into a corporation.” Current shareholders are “the know-how people” and Nanostart Investments AG, Frankfurt am Main. And, he notes, “we are in touch with global players for strategic partnership for marketing of our products in the United States and Asia.”

Reference:
1. Jordan A, Wust P, Fahling H, John W, Hinz A, Felix R. Inductive heating of ferrimagnetic particles and magnetic fluids: physical evaluation of their potential for hyperthermia. Int J Hyperthermia 1993;9(1):51-68