Cancer is no longer restricted to just our bodies. The disease has invaded headlines, pages of books, scientific studies and the public consciousness. Fortunately, however, this non-physiological growth can certainly spark scientific collaborations to fight the bodily form of cancer.
Chemotherapy is but a poison that attempts to destroy all rapidly reproducing cells, taking with it cells of the stomach lining, hair and nails. This toxin weakens the immune system, the liver and, quite often, the patients’ will to fight. Cancer immunotherapy, the medical use of the immune system to fight cancer that was named as “Breakthrough of the Year” by Science, may very well reverse this destructive tendency.
Researchers at the Johns Hopkins School of Medicine have found a way to prepare the immune system with nanotechnology so it can recognize and fight cancerous cells. The secret lies in an iron-based nanoparticle’s properties: They are 50-100 nanometers thick, non-harmful to living tissue and slightly magnetic.
The human immune system, the body’s defense mechanism, must be proficient in differentiating between harmful antigens and harmless cells and tissues of the body. It often does this by differentiating between the potentially harmful nonself and the normally harmless self. Since cancer isn’t a foreign particle, the immune system is rendered helpless to the lethal disease. To make matters worse, the rapidly dividing cells of cancerous tissue are subject to high mutation rates. Thus, even if the immune system could recognize cancer cells, it is unlikely that the defense system would be able to act before the disease evolved into a new form.
The Hopkins researchers have found a way to combine the properties of nanoparticles and the major histocompatibility complexes (MHCs) of the immune system. During an immune system response, MHCs digest antigens that have been destroyed by cells. After digestion, these complexes transport the antigen framents to the cell surface, making the cell an antigen presenting cell (APC). These cells can bind T-cells, immune system cells that recognize antigen displays. Upon T-cell binding, APCs release signals that make the T-cell rapidly divide. This ensures that the T-cell is prepared to attack antigens similar to the one displayed by the APC.
Taking this process into account, the Hopkins researchers added nanoparticles to MHCs presented with specific antigens and antibodies attracted to T-cell receptors. Together, these entities created artificial antigen presenting cells (aAPCs). T-cells for the specific antigens grew in great numbers, assuring a victorious battle against the afflicted cells.
When used against cancerous cells, the weak vasculature created by tumors allowed the aAPCs to escape from the bloodstream and enter the site of tumor origin.
The researchers compared the response of the previously activated T-cells to those of naïve, or unactivated, T-cells. The activated T-cells bound twofold fewer nanoparticles than their naïve counterparts. Furthermore, naïve T-cells are known to have more fine-tuned results in activating the immune system. Finding a way to target the desired area and the correct type of T-cells seemed to be the only aspect missing in the creation of a new type of immunotherapy.
The paramagnetic properties of aAPCs allowed the researchers to use magnetic fields to concentrate the particles in desired areas without significant biological side effects. When aAPCs were clustered around naïve T-cells, the researchers observed a more efficient activation of the immunological response. Proliferation of the aAPC-clustered T-cells increased fourfold compared to nonmagnetic controls. Moreover, antigen-specific T-cells increased between 450- and 3600-fold, a significant laboratory-generated feat in comparison with the natural viral response of a 1000-fold increase.
After these stages, the researchers moved to a living model. They chose transgenic mice with melanoma, a skin cancer. Because this particular cancer is seldom recognized by the immune system, the model created the perfect testing ground for aAPC efficiency. Treatment with both aAPCs and the magnetic field resulted in an eight- to tenfold smaller tumor size than in untreated mice at day 18. By day 28, this treatment had completely removed all traces of tumors in four mice.
Dosage differences and magnetic field timing can be altered to minimize side effects. This makes aAPCs outstanding chemotherapeutic agents. Of course, much more testing must be done before aAPCs can be used for treatment. Furthermore, there are still immune system mechanisms that are not fully understood, and the magnetic properties of nanoparticles have never been used in combination therapy.
As a prime example of human collaboration in attempts to vanquish cancer, the Biomedical and Cell Engineering Departments, with the Departments of Biology, Pathology, Oncology and Medicine have coalesced to yield intriguing results.