A Novel Plant Origin Immunotherapeutic and Anti-Cancer Drug GA-40

Abstract

Search nontoxic naturally-occurring substances that can cause selective destruction of cancer cells directly or by activating antitumor immunity are the two major strategies for development anti-cancer drug discovery. The aim of the studies is to screen Georgian endemic medicinal plants on the content of bioactive peptides with anti-cancer and immunomodulation activity. Their identification, characterization, as well as, conducting  pre-clinical and clinical studies to establish their efficacy and safety for cancer patients. As a result of such works the new immunotherapeutic and anticancer drug GA-40 was created. The drug GA-40 is a standardized complex of bioactive peptides, obtained from a Georgian endemic medicinal plants, which widely used for the treatment of cancer since old times in Georgia. Preclinical and clinical trials have shown that GA-40 does not cause local inflammations, supersensitive reactions, slow type supersensitive reactions, general anaphylaxis,   acute toxicity, and chronic toxicity, specific types of chronic toxicity, immunotoxicity, mutagenic activities, reproductive toxicity, allergic reactions and cumulation. GA-40 does not cause pathological alterations in biochemical, immunological, development of normal antibodies, lipid and carbohydrate metabolism and other indices of peripheral blood. GA-40 does not impact integral indices, cardiovascular and respiratory systems, on the complementary system, and generative functions of the body. GA-40 does not cause morphological and histostructural changes in the external and internal organs of the body: heart, liver, spleen, intestines, pancreas, central nervous system (behavior) and other tissues of the body, as well as the alterations in body temperature and blood pressure. Preclinical and clinical trials have shown that GA-40 destroys malignant tumor cells via apoptosis and unlike chemical preparations has no negative effect on the normal cells (fibroblast, endothelial cells). In vitro studies and clinical trial results show that GA-40 induces differentiation of human myeloid leukemia cells (HL-60) into normal myeloid cells. GA-40 causes the activation of anti-tumor immunity.  Mononuclear cells (MNC) activated by GA-40, produce Tumor Necrosis Factor (TNF-α) and Interferon (INF-γ), which play important role in the destruction and selectively remove cancer cells by the way apoptosis. GA-40 activates cytotoxic-T cells (T-killer cell, CTL), Cytotoxic Macrophages (MF), Neutrophils (NF). GA-40 inhibits the release of vascular epithelial cell growth factor (VEGF) by cancer cells and blocks the development of new blood vessels in malignant neoplasms, preventing tumor growth and spread of metastases. GA-40 shows antioxidant activity, it causes decrease in lactic and pyruvic acids, xanthine, uric acid, hydrogen peroxide, oxygen with two unpaired electrons, hydrogen with one unpaired electron. GA-40 provides for normalization of the blood biochemical indices – total protein, albumin, globulin, urea, nitrogen, creatinine, bilirubin, glucose concentration, as well as certain enzymes activity such as alanine-aminotransferase, aspartate-aminotransferase, gamma-glutamic transpeptidase and alkaline phosphatase. GA-40  restores the functional activity of Hematopoietic stem cells, to normalizing the content of leukocytes, erythrocytes, neutrophils, thrombocytes, lymphocytes and other blood forming elements; The preparation renders a positive influence on the dynamic contents in the bloodstream of carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), prostate-specific antigen (PSA), and other specific markers of a tumor is observed. In conclusion we can say that GA-40 monotherapy or Ga-40 in combination with chemo-radiation therapy inhibits growth of tumor cells and causes regression of the existing tumor and metastases. GA-40 treatment minimizes chemotherapy and radiation therapy causing side effects, exerts immunoprotection, and improves the overall survival, as well as the quality of life in cancer patients. We are convinced, that GA-40 and other specific information carrying bioactive plant peptides in the near future may be a new generation of safe and highly effective holistic preparations in medicine.