ATLANTA—Scientists at Georgia Tech and the Ovarian Cancer Institute have further developed a potential new treatment against cancer that uses magnetic nanoparticles to attach to cancer cells, removing them from the body.
The treatment, tested in mice in 2008, has now been tested using samples from human cancer patients. The results appear online in the journal Nanomedicine.
"We are primarily interested in developing an effective method to reduce the spread of ovarian cancer cells to other organs," says John McDonald, professor at the School of Biology at the Georgia Institute of Technology and chief research scientist at the Ovarian Cancer Institute.
McDonald points out that in the current application, the research team is interested in trying to reduce the frequency of metastasis (spreading of cancer cells from the site of the primary ovarian tumor).
"Much of the spreading of ovarian cancer (OC) is due to cancer cells sloughing off the primary tumor into the abdominal cavity of patients and spreading to secondary sites like the liver," he says. "Our goal is to use magnetic nanoparticles engineered to bind to these 'free floating' OC cells to 'pull' them out of the patient using a dialysis-type system."
McDonald notes that a chamber is being designed where fluid collected from OC patients is captured by the engineered magnetic particles and then trapped in a magnetic field, clearing the fluid of cancer cells before cycling the fluid back into the patient.
"A peptide that specifically binds to a receptor protein we have previously shown to be highly expressed on OC cells is attached to the magnetic nanoparticles allowing the particles to specifically target and bind to the cancer cells," he adds. "In our recent paper, we demonstrate that the particles can be used to successfully remove cancer cells from the ascites (abdominal fluid) of OC patients."
The idea came to the research team from the work of Ken Scarberry, then a Ph.D. student at Georgia Tech. He originally conceived of the idea as a means of extracting viruses and virally infected cells. At his advisor's suggestion, Scarberry began looking at how the system could work with cancer cells.
Scarberry published his first paper on the subject in the Journal of the American Chemical Society in July 2008. In that paper he and McDonald showed that by giving the cancer cells of the mice a fluorescent green tag and staining the magnetic nanoparticles red, they were able to apply a magnet and move the green cancer cells to the abdominal region.
Scarberry points out that that the morbidity of most cancers is less often related to the growth of the initial tumor mass and more often related to the metastatic dissemination of cells sloughing off the primary tumor.
"Following surgical extraction of the tumor, chemical and radiation therapies are typically recommended to kill the residual malignant cells but many lack efficient targeting strategies and often result in damage to surrounding healthy tissues," he explains. "The prognosis and therapies required to treat abdominal cancers could improve significantly if the metastatic cells could be removed from the patient prior to their implantation at distant secondary sites. Magnetic nanoparticles are functionalized with ligands that selectively bind to surface markers that are uniquely expressed by metastatic cells or blood-borne cancers. These selective nanoparticles adsorb to the cancer cell surface and can be selectively removed from bodily fluids."
Now McDonald and Scarberry, currently a post-doc in McDonald's lab, has showed that the magnetic technique works with human cancer cells.
"Often, the lethality of cancers is not attributed to the original tumor but to the establishment of distant tumors by cancer cells that exfoliate from the primary tumor," notes Scarberry. "Circulating tumor cells can implant at distant sites and give rise to secondary tumors. Our technique is designed to filter the peritoneal fluid or blood and remove these free floating cancer cells, which should increase longevity by preventing the continued metastatic spread of the cancer."
Scarberry notes that the technology is being tested against blood-borne and metastatic cancers.
"The technology is applicable when a cancer cell expresses an identifiable marker for which we are able to develop a ligand," he says.
McDonald also points out that the technology will be effective only for "free floating" cancer cells such as OC cells floating in the abdominal fluid of patients or possibly against free floating cancer cells circulating in blood like leukemia cells.
In this latest round of testing, their technique appears to work as well at capturing cancer cells from human patient samples as it did in mice.
Scarberry notes that the research team recently completed a survival study demonstrating the efficacy of the technology at increasing long-term survivorship in an animal model. The next steps will be focused on satisfying FDA requirements necessary to move toward clinical trials.
"We are currently finishing work showing that the technology can actually result in a significant reduction in metastasis in an animal (mouse) model," McDonalds points out. "The next stem would be limited trials in humans."
With regard to drug development, Scarberry notes that the proposed technology is a targeted modality that is minimally invasive and reduces malignant cell burden mechanically, avoiding drug-related issues like collateral damage, side effects and tolerance.
Scarberry adds that it is possible to apply this same technology to other cancer cells or pathogens by using ligands that bind to receptors expressed specifically by those cells or pathogens. So this could be big news across several cancers, not just ovarian.
Moreover, McDonald points out that the technology may be most effective when used in combination with anti-cancer drugs.
"The use of this technology to isolate cancer cells from patients may allow scientists to test the efficacy of specific drugs on cancer cells isolated from individual patients, thereby allowing development of customized therapies," he says. "The systems we have developed to target magnetic nanoparticles specifically to cancer cells may be extended to direct other types of nanoparticles (designed specifically) to carry drugs to cancer cells."
Measuring success of the continued research is simple. McDonald says the key gauge of success is demonstrating that is actually results in a reduction of metastases and extended longevity of OC patients.
"Once we have demonstrated that the technique can have a positive impact on the lives of human cancer patients it will be considered a success," Scarberry concludes.
The treatment, tested in mice in 2008, has now been tested using samples from human cancer patients. The results appear online in the journal Nanomedicine.
"We are primarily interested in developing an effective method to reduce the spread of ovarian cancer cells to other organs," says John McDonald, professor at the School of Biology at the Georgia Institute of Technology and chief research scientist at the Ovarian Cancer Institute.
McDonald points out that in the current application, the research team is interested in trying to reduce the frequency of metastasis (spreading of cancer cells from the site of the primary ovarian tumor).
"Much of the spreading of ovarian cancer (OC) is due to cancer cells sloughing off the primary tumor into the abdominal cavity of patients and spreading to secondary sites like the liver," he says. "Our goal is to use magnetic nanoparticles engineered to bind to these 'free floating' OC cells to 'pull' them out of the patient using a dialysis-type system."
McDonald notes that a chamber is being designed where fluid collected from OC patients is captured by the engineered magnetic particles and then trapped in a magnetic field, clearing the fluid of cancer cells before cycling the fluid back into the patient.
"A peptide that specifically binds to a receptor protein we have previously shown to be highly expressed on OC cells is attached to the magnetic nanoparticles allowing the particles to specifically target and bind to the cancer cells," he adds. "In our recent paper, we demonstrate that the particles can be used to successfully remove cancer cells from the ascites (abdominal fluid) of OC patients."
The idea came to the research team from the work of Ken Scarberry, then a Ph.D. student at Georgia Tech. He originally conceived of the idea as a means of extracting viruses and virally infected cells. At his advisor's suggestion, Scarberry began looking at how the system could work with cancer cells.
Scarberry published his first paper on the subject in the Journal of the American Chemical Society in July 2008. In that paper he and McDonald showed that by giving the cancer cells of the mice a fluorescent green tag and staining the magnetic nanoparticles red, they were able to apply a magnet and move the green cancer cells to the abdominal region.
Scarberry points out that that the morbidity of most cancers is less often related to the growth of the initial tumor mass and more often related to the metastatic dissemination of cells sloughing off the primary tumor.
"Following surgical extraction of the tumor, chemical and radiation therapies are typically recommended to kill the residual malignant cells but many lack efficient targeting strategies and often result in damage to surrounding healthy tissues," he explains. "The prognosis and therapies required to treat abdominal cancers could improve significantly if the metastatic cells could be removed from the patient prior to their implantation at distant secondary sites. Magnetic nanoparticles are functionalized with ligands that selectively bind to surface markers that are uniquely expressed by metastatic cells or blood-borne cancers. These selective nanoparticles adsorb to the cancer cell surface and can be selectively removed from bodily fluids."
Now McDonald and Scarberry, currently a post-doc in McDonald's lab, has showed that the magnetic technique works with human cancer cells.
"Often, the lethality of cancers is not attributed to the original tumor but to the establishment of distant tumors by cancer cells that exfoliate from the primary tumor," notes Scarberry. "Circulating tumor cells can implant at distant sites and give rise to secondary tumors. Our technique is designed to filter the peritoneal fluid or blood and remove these free floating cancer cells, which should increase longevity by preventing the continued metastatic spread of the cancer."
Scarberry notes that the technology is being tested against blood-borne and metastatic cancers.
"The technology is applicable when a cancer cell expresses an identifiable marker for which we are able to develop a ligand," he says.
McDonald also points out that the technology will be effective only for "free floating" cancer cells such as OC cells floating in the abdominal fluid of patients or possibly against free floating cancer cells circulating in blood like leukemia cells.
In this latest round of testing, their technique appears to work as well at capturing cancer cells from human patient samples as it did in mice.
Scarberry notes that the research team recently completed a survival study demonstrating the efficacy of the technology at increasing long-term survivorship in an animal model. The next steps will be focused on satisfying FDA requirements necessary to move toward clinical trials.
"We are currently finishing work showing that the technology can actually result in a significant reduction in metastasis in an animal (mouse) model," McDonalds points out. "The next stem would be limited trials in humans."
With regard to drug development, Scarberry notes that the proposed technology is a targeted modality that is minimally invasive and reduces malignant cell burden mechanically, avoiding drug-related issues like collateral damage, side effects and tolerance.
Scarberry adds that it is possible to apply this same technology to other cancer cells or pathogens by using ligands that bind to receptors expressed specifically by those cells or pathogens. So this could be big news across several cancers, not just ovarian.
Moreover, McDonald points out that the technology may be most effective when used in combination with anti-cancer drugs.
"The use of this technology to isolate cancer cells from patients may allow scientists to test the efficacy of specific drugs on cancer cells isolated from individual patients, thereby allowing development of customized therapies," he says. "The systems we have developed to target magnetic nanoparticles specifically to cancer cells may be extended to direct other types of nanoparticles (designed specifically) to carry drugs to cancer cells."
Measuring success of the continued research is simple. McDonald says the key gauge of success is demonstrating that is actually results in a reduction of metastases and extended longevity of OC patients.
"Once we have demonstrated that the technique can have a positive impact on the lives of human cancer patients it will be considered a success," Scarberry concludes.
