Malignant tissue can be normalized in vitro using mechanical signals. A biomechanical treatment has been applied to a tumor of human origin grafted subcutaneously in mice and demonstrated the normalizing effect of stress on tumor growth in vivo. Following this Proof of Concept, a feasibility study has been performed to build a prototype for a Proof of Efficacy: Application of a Constraint Field on human pancreatic cancer grafted in the pancreas of mice. Two devices are combined to generate the local constraint: First a generator of Gradient of Magnetic Field (GMF), second magnetizable iron nanoparticles located in the neovessels surrounding the tumor itself. Nanoparticles act as bioactuators transforming magnetic energy in mechanical energy. This feasibility study was performed on the GMF generator with two opposite permanent magnets. The pressure (Pa) created on the neovessels is: P = Fv.L.Ms,v.dB/dx
L is the stroma thickness (m);
Fv is the nanoparticle volume proportion of stroma;
Ms,v is the magnetization of nanoparticles (A/m);
dB/dx is the magnetic induction gradient in stroma thickness direction (T/m).
Iron-core coils are the best means to obtain our goal: A magnetic pressure of about 100 to 500 Pa on the tumor surface. The tumor is a one-centimeter-diameter sphere located at the center of our measured zone, a tube with 3 cm square section.
Three dimensional magnetic simulations with a finite element method show that a magnetic induction gradient of 50 T/m is achievable. This gradient can be maintained permanently, can vary with time, and can have a variable direction in the field of study.
The other variables that increase pressure are: The proportion of iron particles (greater than 100 mg/ml), the thickness of stroma, and the magnetization of particles.
The experimental laboratory environment in which the anesthetized rodents are studied must permit heat dissipation to obtain reproducible results with no influence of temperature. The power losses do not exceed 600 watts, so the use of air-cooling is adequate.
The magnetic induction gradients are strong, but obtainable at the tumor-stroma interface. The progression to a whole human prototype will necessarily require supra-conductor coils.
We will present the data on changes in in vivo human tumor size and configuration with the application of external quantifiable constraint field in the experimental mouse.
Citation Format: Remy Brossel. Biomechanics: A new therapeutic innovation deposit – From the proof of concept to the proof of efficacy. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A41.