Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Adjuvant Cancer Therapy, to Complement Immune Checkpoint Therapy and Other Traditional Cancer Therapies, with Least Auto-immune Side Effects through Eco-balance of Human Microbiome
DOI:
https://doi.org/10.37285/ijpsn.2018.11.6.3Abstract
This paper describes a novel serendipitous discovery to successfully treat cancer with improved efficiency emerged while using Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy (originally discovered to prevent or treat nosocomial infections) as an adjuvant therapy along with the immune checkpoint therapy and other conventional cancer therapies. This new discovery is named as “Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Adjuvant Cancer Therapy”. Cancer is rising as a global epidemic, currently killing over 9 million people every year. This figure is supposed to get up to 13 million by the year 2030. The cancer epidemic is more prevalent in the Western countries than Eastern countries. The cost of treating cancer was $290 billion in the year 2010 and it is supposed to get up to $458 billion/year by the year 2030. Recently checkpoint immune therapy is showing great promise as a treatment tool. Yet the global success in treating the cancer is only 20% or slightly higher, with all the advancements and discoveries. A new paradigm shift in cancer treatment has been discovered as serendipitous discovery to enhance the efficiency of the existing cancer therapies significantly. This serendipitous discovery came as a surprise while running community based clinical trials using the novel discovery of Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy to prevent or cure the hospital acquired or nosocomial infections, which are affecting over six million people with severe mortality. Several physicians have observed that Dr. Reddy’s Probiotic therapy given for prevention or control of nosocomial infections significantly helped the recovery of cancer patients who were also receiving standard cancer therapies. This article outlines the mechanism by which Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy assist to cure cancer at a much faster pace, with the least side effects, when used as adjuvant therapy along with the immune checkpoint therapy, and other standard cancer therapies. Details are presented how the PD-1 and CTLA-4 blockade therapy works to reduce cancer and also the possible scientific explanations why such an immune checkpoint therapy only works on limited cancer cases. The effect of Multiple Mixed Strain Probiotics on establishing the immune tolerance through reduction of local or systemic inflammation is also outlined. The possible biological and immunological mechanisms of how Multiple Mixed Strain Probiotic Therapy significantly enhances the immune checkpoint therapy (PD-1 and CTLA-4 blockade) has been presented with explicit details. The details are also presented showing how Multiple Mixed Strain Adjuvant Therapy can minimize or significantly reduce the unpleasant side effects of the current conventional and immune checkpoint cancer therapies. Practical clinical and experimental data presented to show the significance of Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy, as an adjuvant therapy, along with the standard cancer therapies to improve the cancer treatment efficiencies by up to 60%. Evidence is presented to illustrate and point out that the current FDA regulations will allow the use of Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic (Therapy) as nutritional supplement, since the probiotic strains used are categorized as food grade and GRAS (Generally Regarded as Safe), as per the 21 Code of Federal Regulations of the Food and Drug Administration. Details are presented with genus and species identification of individual probiotic strains used in the Multiple Mixed Strain Probiotic Therapy. Thus special and formal FDA approval is not required to use them as adjuvants to improve the efficiency of traditional cancer therapies. Finally the scientific reasoning is presented with evidence to illustrate the utmost urgency and necessity of using Dr. M.S. Reddy’s “Multiple Mixed Strain Probiotic Therapy” along with the immune checkpoint therapy and other traditional cancer therapies to protect the lives of millions of people dying with cancer annually.
Downloads
Metrics
Keywords:
Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy, immunomodulins, bacteriocins, Probiotics, PD-1 receptor, PD-L1 ligand, PD-1/PD-L1 blockade therapy, CTLA-4 blockade therapy, immune checkpoint therapy, standard cancer therapy, effector T-cells, T-reg cells, immunomodulation, immune tolerance, bio-available calcium, Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Adjuvant Cancer Therapy.
Downloads
Published
How to Cite
Issue
Section
References
Das S, Suarez G, Beswick EJ, Sierra JC, Graham DY and Reyes VE (2006). Expression of B7-H1 on gastric epithelial cells: its potential role in regulating T-cells during Helicobacter pylori infection. J Immunol 176(5): 3000-3009.
Derks S, Liao X, Chiaravalli AM, Xu X, Camargo MC and Solcia E (2016). Abundant PD-L1 expression in Epstein-Barr-infected gastric cancers. Oncotarger 7(22):32925.
Doug H, Zhu G, Tamada K and Chen L (1999). B-7H1, a third member of the B family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med 5(12): 1365-1369.
Doug H, Stome SE, Salomao DR, Tamura H, Hirano F and Flies DB (2002). Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8(8): 793-800.
Engels B, Engelhard VH, Sidney J, Sette A, Binder DC and Liu RB (2013). Relapse or eradication of cancer is predicted by peptide-major histocompatibility complex affinity. Cancer Cell 23(4): 516-526.
Fang W, Zhang J, Hong S, Zhan J, Chen N and Qin T (2014). EBV-driven LMP1 and IFN –y up-regulates PD-L1 in nasopharyngeal carcinoma: implications for oncotargeted therapy. Oncotarget 5(23): 12189.
Frankel AE, Coughlin LA, Kim J, Froehlich TW, Xie Y and Frenkel EP (2017). Metagenomics shotgun sequencing and unbiased metabolomics profiling identity specific human gut microbiota and metabolites associated with immune checkpoint therapy efficacy in melanoma patients. Neoplasia 19(10): 848-855.
Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T and Nishimura H (2000). Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192(7): 1027-1034.
Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Melenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Cololins M, Wood CR and Hanjo T (2000). Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to a negative regulation of lymphocyte activation. J Exp Med. 192(7): 1027-1034.
Golden-Mason L, Palmer B, Klarquist J, Mengshol JA, Castelblanco N, Rosen HR (2007). Upregulation of PD-1 expression on circulating and intrahepatic hepatitis C virus-specific CD8+ T-cells associated with reversible immune dysfunction. J Virol 81(17): 9249-9258.
Hapmton T (2018). Gut microbes may shape response to cancer immunotherapy. JAMA 319(5): 430-431.
Hironiwa N, Ishii S, and Hattori K (2016). Calcium dependent antigen binding as a novel modality for antibody recyceling by endosomal antigen dissociation. MAbs 8 (1): 65-73.
Idhida M, Tanaka Y, Okazaki T, Freeman GJ and Minato N (2002). Differential expression of PD-1 and PD-L2, ligand for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues, Imunol Lett 84(1): 57-52.
Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T and Minato N (2002). Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA 99(19): 12293-12297.
Iwai Y, Terawaki S and Honjo T (2004). PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T-cells. Int. Immuonl. 17(2): 133-144.
Keri ME, Butte MJ, Freeman GJ and Sharpe AH (2008). PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 26: 677-704.
Leach, DR, Krummel MF and Allison JP (1996). Enhancement of antitumor immunity by CTLA-4 blockade. Science 271(5256): 1734-1736.
Livingston M, Loach D, Wilson M, Tannock G and Baird M (2009). Gut commensal Lactobacillus reuteri 100–23 stimulates an immunoregulatory response. Immunol Cell Biol 88: 99-102.
Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y and Alegre ML (2018). The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359(6371): 104-108.
Mazanet MM and Hyghes CC (2002). B-7-H1 is expressed by human endothelial cells and suppresses T-cell cytokine synthesis. J Immunol 169(7): 3581-3588.
Muhlbauer M, Fleck M, Shutz C, Weiss T, Froh M and Blank C (2006). PD-L1 is induced in hepatocytes by viral infection and by interferon-x and y and mediates T-cell apoptosis. J Hepatol 45(4): 520-528.
Okada H, Kuhn C, Feillet H and Bach J (2010). The hygiene hypothesis for autoimmune and allergic diseases: an update. Clin Exp Immunol 160: 1-9.
Peng G, Li S, Wu W, Tan X, Chen Y (2008). PD-1 upregulation is associated with HBV-specific T-cell dysfunction in chronic hepatitis B patients. Mol Immunol 45(4): 963-970.
Reddy MS, Washam CJ, Reinbold GW and Vedamuthu ER (1973). Immunogenic properties of slime from Propionibacterium. J Milk Food Technol 36: 200-201.
Reddy MS, Reddy DRK, and Pradad Nav (2000). Herbal and pharmaceutical drugs enhanced with Probiotics. US patent 6080401: 1-48.
Reddy MS and Reddy DRK (2007) Improving the health and longevity with Probiotics and Ayurveda. J Am Bharathi-ATA 1: 16-27.
Reddy MS and Reddy DRK, (2004). Probiotics, biotechnology, and Ayurvedic herbs - complementary and alternative medicine. AAPI (American Association of Physicians of Indian Origin) Journal/May/June, pp-32-33.
Reddy MS, Reddy DRK (2005). Proyurveda (Probiotics + Ayurveda) on curing the acute and chronic diseases, without any side effects – integrated medicine program. Presented at the 23rd annual AAPI (American Association of Physicians of Indian Origin), June 15-19, Houston, Texas, USA.
Reddy MS, Reddy DRK (2007). Probiotics in health and disease vs. Proyurveda (Probiotics L. acidophilus DRK, B. bifidus MS and Prebiotic – Ayurvedic herbs) in health and disease, clinically tested over million human subjects. Presented at 25th (Silver Jubilee) medical convention of AAPI (American Association of Physicians of Indian Origin) (integrated medicine program on combining Ayurveda into clinical practice), May 9-13, Philadelphia, Pennsylvania, USA.
Reddy MS and Reddy DRK (2009). Probiotic therapy. AAPI (American Association of Physicians of Indian Origin) Journal 3: 28-29.
Reddy MS and Reddy DRK (2011). Antiaging: a review and experimental clinical study of bioavailable calcium, probiotics, and their effect on reversing osteopenia, osteoporosis, and other common health conditions. Int. J Pharma Sci Nanotech: 4: 1436-1444
Reddy MS and Reddy DRK (2015). Therapeutic Probiotics for cancer reduction. AAPI (American Association of Physicians of Indian Origin) Journal 06: 36-39.
Reddy MS and Reddy DRK (2016). Development of Multiple Mixed Strain Probiotics for “Probiotic therapy” under clinical conditions, to prevent or cure the deadly hospital acquired infections due to Clostridium difficile (C. diff) and Methicillin Resistant Staphylococcus Aureus (MRSA). Int J Pharma Sci Nanotech 9: 3256-3281.
Reddy MS and Reddy DRK (2016). Isolation and determination of the major principle of causative agent behind the 2016 published breakthrough discovery of Dr. M.S. Reddy’s “Multiple Mixed Strain Probiotic Therapy” in successfully treating the lethal hospital acquired infections due to Clostridium difficile (C. diff) and Methicillin Resistant Staphylococcus Aureus (MRSA). Int J Pharma Sci Nanotech 6: 3556-3566.
Reddy MS and Reddy DRK. (2016). Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy. J Pharmaceutics and Nano Technol. Vol. 4 Issue (3): 15-28.
Reddy MS and Reddy DRK (2017). An insight into the 2016 Best Medical awardWinning Breakthrough Microbial and Nano-technology based discovery of Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy, to successfully treat the Nosocomial infections. Nanotechnol and Nanosci J 1(1): 2-5.
Reddy MS (2017). An approach to osteopenia and osteoporosis. AAPI (American Association of Physicians of Indian Origin) Journal (fall issue): 26-27.
Reddy MS (2017). Importance of bio-available calcium and other mineral to reduce the calcium deficiency symptoms, aging, and other pertinent diseases. Clin Pharmacol biopharma 6(2):1-5.
Reddy MS (2017). Chronic stress-an etiological agent for the genesis of multitude of diseases, and the effect of meditation on modulating the stress. Open Acc J of Toxicol 1(5): 555-571.
Reddy MS (2018). A Multiple Mixed Probiotic Therapy to treat or prevent hospital acquired infections. AAPI (American Association of Physicians of Indian Origin) journal. Spring 2018: 38.
Reddy MS (2018). Immunomodulatory effect of “Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy” to cure or prevent hospital acquired nosocomial infections due to Clostridium difficile (C. diff), other pathogenic bacteria, and autoimmune diseases. Int J Pharma Sci Nanotech 11(1): 3937-3949.
Saavedra JM and Bauman NA (1994). Feeding of Bifdobacterium bifidum and Streptococcus thermophillus to infants in hospital for prevention of diarrhea and shedding of rotavirus. Lancet 344: 1046-1049.
Selenko-Gebauer N, Majdic O, Szekeres A, Hofler G, Guthann E and Korthauer U (2003). B7-H1 (programmed death-1 ligand) on dendritic cells is involved in the induction and maintenance of T-cell anergy. J Immunol 170(7): 3637-44.
Shen T, Chen X, Chen Y, Xu Q, Lu F, Lie S (2010). Increased PD-L1 expression and PD-L1/CD86 ratio on dendritic cells were associated with impaired dendritic cells function in HCV infection. J Med Virol 82(7): 1152-1159.
Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K and Earley ZM (2015). Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-Pd-L1 efficacy. Science 350(6264): 1084-1089.
Solis-Pereyra B and Lemonnier D (1993). Induction of human cytokines by bacteria used in dairy foods. Nutr Res 13: 1127-1140.
Tamura H, Dong H, Zhu G, Sica GL, Flies D and Tamada K (2001). B-7-H1 constimulation preferentially enhances CD28-independent T-helper cell function. Blood 97(6):1809-16.
Thiel M, Wolfs M, and Hoth M (2010). Efficeincy of T-cell costimulation by CD80 and CD86 cross-linking correlates with calcium entry. Immunology 129 (1): 28-40.
Wang, Y, MA R, Lee SA and Zang L (2018). Modulation of gut microbiota: A novel paradigm of enhancing the efficacy of programmed death – 1 and programmed death ligand – 1 blockade therapy. Front Immunol 9: 374 (1-13).
Wargo JA, Gopalakrishnan V, Spencer C, Karpinets T, Reuben A, and Andres MC (2017). Association of the diversity and composition of the gut microbiome with responses and survival (PFS) in metastatic melanoma (MM) patients (pts) on anti-PD-1 therapy. J Clin Oncol 35(15): 3008.
Wu YY, Lin CW, Cheng KS, Lin C, Wang YM and Lin IT (2010). Increased programmed death-lingand-1 expression in human gastric epithelial cells in Helicobacter pylori infection. Clin Exp Immunol 161(3): 551-559.
Xie Z, Chen Y, Zhao S, Yang Z, Yao X and Guo S (2009). Intrahepatic PD-1/PD-L1 up-regulation closely correlates with inflammation and virus replication in patients with chronic HBV infections. Immunol Incest 38(7): 6.
Yamazaki T, Akiba H, Iwai H, Matsuda H, Aoki M and Tanno Y (2002). Expression of programmed death 1 ligands by murine T-cells and APC. J Immunol 169(10): 5538-45.
Yang W, Song Y, Lu YL, Sun JZ, Wang HW (2013). Increased expression of programmed death (PD)-1 and its ligand PD –L1 correlates with impaired cell-mediated immunity in high-risk human papillomavirus-related cervical intraepithelial neoplasia. Immunology 139(4): 513-522.
