RECNAC Cancer Research Update

By Joseph Casciari, Ph.D.

The RECNAC project marked its 10th anniversary in February with a Lunch and Lecture presentation at The Center for the Improvement of Human Functioning International. The RECNAC project got its name from Zelma, a former public health nurse and breast cancer patient who survived fourteen years since using The Center’s approach after a lumpectomy. RECNAC is cancer spelled backwards, and the project’s stated goal has been to reverse the increased incidence of cancer worldwide by learning why cancer develops and how it can be

Twenty metastatic renal cancer patients will be treated free of charge for a one year period.

safely treated and prevented. While the goal has not yet been reached, RECNAC scientists have made progress in developing novel therapeutic approaches to fight cancer. The 10th anniversary presentation highlighted protocols developed from RECNAC research that are now nearing or entering the clinical stage.

Dr. Hugh D. Riordan, RECNAC Project Director, began the lecture by sharing a case study of a woman with metastatic renal (kidney) cancer, a form of cancer not yielding to conventional therapies. After undergoing treatment with a combination of high dose ascorbate and other nutrients, as per a protocol based on RECNAC research, this patient is now cancer free. Her success, and that of others, has led the RECNAC project to announce the commencement of a phase I clinical trial using this protocol. Twenty metastatic renal cancer patients will be treated free of charge for a one-year period. The Center is currently seeking patients for this trial.

What makes the RECNAC project unique, according to Project Manager Neil Riordan, is the mandate to achieve its goals within an eleven year time frame. This has encouraged the project’s twelve scientists to focus on therapeutic strategies that can be taken to the clinic in a timely fashion. Riordan mentioned three areas of RECNAC research that are beginning or nearing the clinical trial state: the use of plant and bacterial extracts that inhibit tumor growth and angiogenesis, the use of high dose vitamin C in combination with lipoic acid and other antioxidants’ and immune therapies based on dendritic cells and cytokines produced by white blood cells.

In an ongoing effort to isolate new anti-cancer agents from natural sources, the RECNAC project has developed two extracts that are candidates for clinical trials. Experiments were first conducted to test the ability of these extracts to kill tumor cells, stimulate immune cells, and prevent angiogenesis, the process whereby tumors induce new capillaries to grow toward them. After these in vitro screening studies, the most promising extracts were tested in animal tumor models at the Beijing Tumor Institute. Dr. Xiao Long Meng shared recent results of animal studies with a novel bacterial cell wall extract. This extract inhibited tumor growth in vivo by eighty percent at doses non-toxic to host mice. To illustrate the safety of this extract, Dr. Meng compared it to cyclophosphamide, a commonly used chemotherapeutic agent. The dose of the bacterial extract that was lethal to half of the treated animals was roughly twenty-five times higher than that of cyclophosphamide. Moreover, tumor growth inhibition was achieved at concentrations fifty times lower than the lethal dose. Because of this combination of efficacy and safety, this bacterial extract is being considered along with the plant extract Dr. Meng described at the 1998 RECNAC update for Phase I clinical trials in the near future.

Dr. Riordan has been interested in the use of intravenous vitamin C as an anti-cancer agent for 20 years. Vitamin C is thought to improve immune system function, strengthen the extracellular matrix, and improve patient wellbeing. In addition, it has been shown to be preferentially toxic to tumor cells at high doses. The main question for RECNAC scientists has been whether the doses required for tumor toxicity can be safely reached during IV administration. Dr. Casciari presented a detailed analysis of this issue. Vitamin C concentrations required to kill tumor cells grown in three dimensions were compared to pharmacokinetic data on ascorbate (vitamin C) levels attained during infusion. The analysis revealed that vitamin C at safe and achievable doses was toxic to tumor cells when combined with lipoic acid, an antioxidant that increases vitamin C efficacy. Dr. Casciari presented three case studies on cancer patients treated with a combination of vitamin C and lipoic acid. Some benefit was obtained in all three cases, including stabilization of platelet counts in one patient and a nine-fold decrease in tumor marker levels in another. One of the patients has been cancer free for the past eight months. The Center is thus planning to use the combination of vitamin C and lipoic acid together with immune stimulators in a Phase 1 clinical trial with metastatic renal cancer patients.

RECNAC scientists are also working to improve the immune system’s response against cancer. To highlight the importance of immune response, Neil Riordan sited a study indicating that breast cancer patients who demonstrated some immune reaction against their tumor cells had a much better prognosis than those who did not. Dr. Casciari then provided an update of RECNAC immunotherapy system research. The goal of this research is to stimulate the cell mediated arm of the immune system. Cell mediated immunity involves the recognition and killing of altered host cells, including tumor cells, by T-lymphocytes. One method for stimulating cell mediated immunity is to administer cytokines or other biological response modifiers, including some of the natural product extracts described above, to patients. Cytokines are chemical substances that trigger and regulate immune response. RECNAC is in the process of developing protocols for using a patient’s own blood cells to produce cytokines that stimulate cell mediated immunity.

Another approach toward immunotherapy involves the ex vivo growth of dendritic cells. Dendritic cells are antigen presenting cells responsible for training T-lymphocytes to recognize tumor cells as targets. RECNAC scientists have succeeded in growing mature dendritic cells from patient blood samples, and have demonstrated that these dendritic cells can induce T-lymphocytes to mount an immune response against tumor cells in the laboratory. Immunotherapy research will be a major focus of the RECNAC project in the coming year. To this end, a small clinical research facility in San Jose, Costa Rica, has been established to more rapidly assess the clinical applicability of immunotherapy. Limited clinical trials began last year and will be expanded during 1999.

To receive a video tape of the informative RECNAC research presentation, see the order form on page 7.