LONDON, Ontario — Many cancers will develop resistance to a variety of anticancer drugs, even though they might have been exposed to only one. Multiple-drug resistance (MDR) is a serious obstacle to the successful treatment of cancers and infections. Increased expression of certain proteins on the membranes of resistant cells is believed to be a key contributor to this phenomenon. The challenge for biopharmaceutical companies is therefore to design suitable cancer therapies that will overcome MDR while leaving healthy cells intact.
One emerging Canadian biopharmaceutical company, Bioniche Inc., believes that it has developed an exciting potential cancer therapy that can do this. According to Nigel Phillips, senior vice president of scientific affairs at the company, Bioniche has demonstrated early-stage results involving two distinct activity pathways for the treatment of cancer.
In addition to stimulating a profound immune response, Mycobacterial Cell Wall Complex (MCC) — which is the active ingredient in Bioniche's lead drug candidate, Regressin — proved capable of directly killing cancer cells, with a mode of action usually associated with chemotherapeutic agents. To a varying degree, all of the cancer cell lines the company has so far tested entered a state of apoptosis after exposure to MCC.
Normal Cells Spared Apoptosis
Research results also indicate that, unlike conventional chemotherapy, MCC does not appear to induce apoptosis in normal cells. The range of cancer cell lines tested included human leukemia cells, human colon cancer cells, human bladder cancer cells and human esophageal cancer cells.
Phillips said the studies, which have received favorable review at several scientific conferences, demonstrated that MCC, a cell wall DNA complex prepared from the non-pathogenic microorganism Mycobacterium phlei, induces apoptosis in a wide variety of cancer cells, independent of MDR or p53 mutations. MDR and p53 mutations are found in a large proportion of all cancers, and their presence is associated with a significant decrease in the effectiveness of cancer chemotherapy and radiation therapy.
The ability of MCC and the associated DNA to induce apoptosis in cancer cells that are unresponsive to chemotherapy and radiation therapy signifies a breakthrough that is of considerable importance for patients who have previously failed conventional treatments.
"We have already established that Regressin is a potent stimulator of the synthesis of the anticancer cytokine interleukin-12, which indirectly inhibits tumor cell proliferation through a number of immunological and non-immunological pathways." Phillips said. "We now know that inhibition of tumor cell growth and induction of apoptosis can occur in direct response to the MCC in Regressin."
Company Expanded Laboratory Facilities
In results from a Phase II/III Canadian clinical trial, Regressin already has demonstrated both safety and efficacy in the treatment of carcinoma in situ in human bladders. In this multicenter study, not only did Regressin produce a highly significant 50 percent complete response — total tumor remission — but it clearly demonstrated a high degree of complete response (38 percent) in patients who had failed to respond to conventional therapy. Bioniche this year has filed three U.S. patent applications and corresponding international applications for MCC that reflect the advances made in the development of the technology. The company is currently in the final stages of preparation for a multicenter international study, with clinical trials targeted to begin by next January.
As part of this increase in clinical trial activities, the company has expanded its laboratory facilities within a recently completed new wing at the Biotechnology Research Institute of the National Research Council of Canada, in Montreal. Bioniche is one of 14 companies taking advantage of this C$17.6 million (US$11.3 million), 50,000-square-foot facility in one of Canada's premier biotechnology research centers.
Bioniche also has successfully commercialized two proprietary products based on hyaluronic acid: Cystistat for interstitial cystitis, a painful, debilitating bladder condition; and Suplasyn for osteoarthritis. *