SILVER SPRING, Md.—Ascites, which is the buildup of fluid in the abdominal cavity, is called malignant ascites when caused by cancer and accounts for 10 percent of people with ascites. Malignant ascites appears most often in people with breast, colon, liver, gastrointestinal tract, ovarian, pancreatic and uterine cancers. Research is being performed by Arizona-based Translational Drug Development (TD2) under the guidance of pancreatic cancer expert Dr. Daniel D. Von Hoff and funded by Silver Spring, Md.-based PharmaCyte Biotech Inc., a clinical-stage biotechnology company focused on developing targeted treatments for cancer and diabetes using its signature—and patented—live-cell encapsulation technology, Cell-in-a-Box.
Cell-in-a-Box, as described by PharmaCyte Chief Operating Officer and Director Dr. Gerald Crabtree, is a unique process that suspends cells in a solution of sodium cellulose. The suspension is then put through a droplet forming process that results in 0.7 mm particles (about the size of a pinhead), Crabtree notes.
“Cellulose is bioinert in the human body,” Crabtree states, “and the capsules stay intact for up to two years.” Other encapsulating materials such as chitosan and agarose are essentially “blobs” that fall apart.
Cell-in-a-Box technology will be used as a platform upon which treatments for several types of cancer—including advanced, inoperable pancreatic cancer—and diabetes are being built. PharmaCyte Biotech’s treatment for pancreatic cancer involves low doses of the well-known anticancer prodrug ifosfamide, together with encapsulated live cells, which convert ifosfamide into its active or “cancer-killing” form. These capsules are placed as close to the cancerous tumor as possible to enable the delivery of the highest levels of the cancer-killing drug at the source of the cancer. This “targeted chemotherapy” has proven remarkably effective in past clinical trials.
“Remarkably effective?” DDNews asked. Crabtree explains that in early trials, the Pharmacyte capsules, compared to the current gold standard, extended median survival from eight months to 11 months. One-year survival was also slightly better, Crabtree notes, and there were no treatment-related side effects. A major trial is now planned to begin later this year to take place in Australia wherein the number of treatment cycles will be increased from the two used in the previous study.
The TD2 study is designed to determine whether PharmaCyte Biotech’s pancreatic cancer treatment can slow the accumulation of malignant ascites fluid. This pancreatic cancer treatment is a combination of low doses of the cancer prodrug ifosfamide coupled with Cell-in-a-Box capsules, again containing live cells capable of converting ifosfamide into its cancer-killing form.
In an initial study, mice given an aggressive human ovarian cancer (ES-2), which produces significant amounts of malignant ascites fluid, were divided into four groups. There were 10 mice in each group. The mice in Group 1 served as a control group, while Group 2 was made up of mice treated with PharmaCyte Biotech’s pancreatic cancer treatment. Group 3 was treated with cisplatin, a chemotherapy drug often used to treat ovarian cancer, and Group 4 was treated with a combination of PharmaCyte Biotech’s pancreatic cancer treatment and cisplatin.
A follow-up study will use the same ES-2 ovarian cancer model. In this study, the mice will be divided into 12 different treatment groups, with 10 mice in each group. The follow-up study is designed to better define the parameters that will be needed to design a future Phase 1 clinical trial in humans that suffer from malignant ascites fluid accumulation as a result of their abdominal cancers. This follow-up study, also designed by Von Hoff (in conjunction with scientists affiliated with PharmaCyte Biotech), will be conducted by TD2 in the United States.
“We are looking forward to the results of this expanded preclinical study of the effectiveness of our pancreatic cancer treatment in reducing the rate of malignant ascites fluid accumulation in the abdomen. If successful, it could quickly lead to a clinical trial in patients with abdominal tumors, such as in the case of ovarian cancer, who suffer from this very serious cancer-associated malady,” commented Kenneth L. Waggoner, CEO of PharmaCyte Biotech.
Researchers at PharmaCyte expect that their pancreatic cancer treatment will ultimately prove to be effective in slowing the accumulation of malignant ascites fluid and, thus, reduce the number of withdrawals of the fluid that patients must endure over a given period of time. The hope is to help patients who face accumulation of ascites fluid, which is problematic for patients with an abdominal cancer, because it is painful and can cause breathing and other serious problems. Once ascites fluid gets to a certain level, it must be removed on a regular basis. This procedure in itself is very uncomfortable for patients and costly.
PharmaCyte Biotech is also working toward improving the quality of life for patients with advanced pancreatic cancer, including relief from pain, and on treatments for other types of solid cancerous tumors. In addition, PharmaCyte is developing treatments for cancer based upon chemical constituents of the Cannabis plant, known as cannabinoids. In doing so, the company is examining ways to exploit the benefits of Cell-in-a-Box technology in optimizing the anticancer effectiveness of cannabinoids, while minimizing or outright eliminating the debilitating side effects usually associated with cancer treatments. This provides PharmaCyte Biotech the rare opportunity to develop “green” approaches to fighting deadly diseases, such as cancer of the pancreas, brain and breast, which affect hundreds of thousands of individuals worldwide every year.