Science Behind Immunotherapy

Pan Am Cancer Immune Therapy Program

The basis of the 15 day Pan Am Cancer Immunotherapy protocol is serially stimulating various arms of the immune system in order to generate a synergistic attack on the tumor.  The protocol involves initial administration of ImmunoMax, a stimulator of the innate immune system.  Cells of the innate immune system have been shown by many studies to possess the ability to kill cancer cells [1, 2].  Unfortunately in cancer patients the tumor produces factors that “turn off” the immune system [3, 4].  Administration ImmunoMax overcomes the tumor produced inhibitory factors so that the innate immune system cells become activated to start killing the tumor [5].

In order to accelerate the killing of the tumor, intravenous vitamin C is administered.  Studies from the NIH have shown that only intravenous and not oral administration of vitamin C can lead to direct tumor killing [6, 7].  Intravenous vitamin C has been demonstrated by itself to extend patient survival in clinical trials [8, 9].  We believe that the alternation of administration between ImmunoMax and intravenous vitamin C will result not only in a synergistic tumor killing effect but also potently position the innate immune cells to stimulate the adaptive immune response.

The adaptive immune response is comprised of T cells and B cells.  This component of the immune response is needed to establish immunological memory in order to kill residual tumor cells and prevent tumor relapse.  T cells are activated by macrophages and dendritic cells (DC).  T Cell Modulator (TCM) is a small molecule drug that stimulates T cell activation and production of cytokines.  By administration of TCM, the T cells that are stimulated by the innate immune system are further stimulated by TCM.  One of the major issues in cancer is that T cells are not properly stimulated.  By using this combination approach, we have the possibility of overcoming the tumor associated immune suppression.

One other potent weapon in the current protocol is the utilization of patient-specific DC.  The DC is one of the most potent stimulators of the T cell.  Statistically significant efficacy data supports that DC alone prolong survival in some types of cancer [10]. In cancer patients the DC is paralyzed by the tumor.  As part of the current protocol, patient blood is drawn and DC are generated in the laboratory.  The generation and activation of DC outside of the body allows for administration of a potent immune cell which assists in the stimulation of T cell activation, thus leading to tumor eradication.

References

  1. Sui, Q., et al., NK cells are the crucial antitumor mediators when STAT3-mediated immunosuppression is blocked in hepatocellular carcinoma. J Immunol, 2014. 193(4): p. 2016-23.
  2. Mentlik James, A., A.D. Cohen, and K.S. Campbell, Combination immune therapies to enhance anti-tumor responses by NK cells. Front Immunol, 2013. 4: p. 481.
  3. Noy, R. and J.W. Pollard, Tumor-associated macrophages: from mechanisms to therapy. Immunity, 2014. 41(1): p. 49-61.
  4. Mao, Y., I. Poschke, and R. Kiessling, Tumour-induced immune suppression: role of inflammatory mediators released by myelomonocytic cells. J Intern Med, 2014. 276(2): p. 154-70.
  5.  Ghochikyan, A., et al., Targeting TLR-4 with a novel pharmaceutical grade plant derived agonist, Immunomax(R) , as a therapeutic strategy for metastatic breast cancer. J Transl Med, 2014. 12(1): p. 322.
  6. Chen, Q., et al., Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci U S A, 2008. 105(32): p. 11105-9.
  7.  Parrow, N.L., J.A. Leshin, and M. Levine, Parenteral ascorbate as a cancer therapeutic: a reassessment based on pharmacokinetics. Antioxid Redox Signal, 2013. 19(17): p. 2141-56.
  8.  Ma, Y., et al., High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med, 2014. 6(222): p. 222ra18.
  9. Monti, D.A., et al., Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PLoS One, 2012. 7(1): p. e29794.
  10. Mark, D., et al., in Outcomes of Sipuleucel-T Therapy. 2011: Rockville (MD).