Cancer and Immunology

Our research team’s first area of intense focus was in the treatment of cancer.  Our efforts to devise treatments for cancer that work with the body instead of against it included biological response modifiers to stimulate immune response, ex vivo cultivation and anti-cancer antigen training of dendritic cells, tumor angiogenesis (blood vessel growth) inhibition, and the use of intravenous vitamin C (along with lipoic acid, in some cases) as a “gentle” anti-cancer agent and adjuvant.

Our interest in immunotherapy began with our dendritic cell research in the late 1990s.  Under Dr. Neil Riordan’s supervision, we developed techniques for isolating dendritic cells from whole blood and “training” them to respond to tumor antigens.  The technology we developed was eventually licensed to a private firm.

In addition we analyzed the white blood cell bio-energetics in healthy and ill subjects by measuring mitochondrial potentials and ATP levels of whole blood lymphocytes and granulocytes.  These assays were as diagnostic tools or as outcome metrics for immunotherapy. The results of our studies were published in journals:

• Assessment of granulocyte activity with application to healthy and ill subjects. Mikirova N, Riordan H, Klykov A. Orthomolecular Medicine, 2002, 17(3):151-161
• Monitoring of ATP levels in red blood cells and T cells of healthy and ill subjects and the effects of age on mitochondrial potential. Mikirova N, Riordan H, Kirby K, Klykov A, Jackson J. Orthomolecular Medicine, 2005, 20(1):50-58
• Granulocyte activity in patients with cancer and healthy subjects. Mikirova N, Klykov A, Jackson J, Riordan N. Cancer Biology and Therapy, 2008, 7(9):41-46

As vitamin C is thought to be vital for the maintenance of proper immune system functioning, we studied if and how vitamin C supplementation correlates with immune cell performance in white blood cells collected from healthy adults. Specifically, the ability of phagocytes to digest bacteria, the ability of lymphocytes to proliferate in response to PHA, the ability of monocytes to develop into mature antigen trained dendritic cells, and the ability of dendritic cell trained lymphocytes to lyse tumor cells were

determined ex vivo. Phagocytic index, lymphocyte proliferation index, and mature dendritic cell yields (from monocytes) all decreased with donor age in a statistically significant fashion. However, once the effect of donor age is accounted for, immune cell performance was superior in cells from donors who supplemented with at least 1 g per day of vitamin C. The addition of 5 to 20 mg/dL sodium ascorbate to the growth medium during ex vivo assays improved the ability of phagocytes to digest bacteria and

increased the tumor cell killing capabilities of dendritic cell trained lymphocytes.

Effect of Vitamin C Supplementation on Ex Vivo Immune Cell Functioning. Joseph J. Casciari,  Hugh D. Riordan, Nina Mikirova, Jan Austin. JOM, 18, 2, 2003.