Dr. Mohammad Nazam Ansari PhD, Pharmacology

Immunostimulants

Immunostimulants Immuno-stimulants are the substances (drugs and nutrients) that stimulate the immune system by inducing activation or increasing activity of any of its components. These drugs are specifically used to enhance the body immunity. Uses: Immunodeficiency disorders Chronic infections Cancer

Specific Immuno-stimulants Levamisole Thalidomide Recombinant Cytokines  Interferons  Interleukin-2 Immunization  Vaccines, Immune Globulin, Rho (D) Immune Globulin Other drugs  Inosiplex, Azimexon, Imexon, Thymosin, Methylinosine Monophosphate

Levamisole Originally Antihelminthic (drugs that expel parasitic worms) Restores depressed immune function of B cells, T cells, Monocytes, Macrophages USES Adjuvant therapy with 5-FU in colon cancer Immunodeficiency associated with Hodgkins disease. Toxicity Fatal Agranulocytosis

Thalidomide Enhance T-cell production of cytokines – IL-2, IFN-γ NK cell-mediated cytotoxicity against tumor cells Causes birth defect Contraindicated in women with childbearing potential USE: Multiple myeloma

Recombinant Cytokines Antiviral Immunomodulatory activity Bind to cell surface receptors – initiate intracellular events  Enzyme induction  Enhancement of immune activities  Increased Phagocytosis

Interferon (INF): INF-α,β,γ Antiviral, anticancer, immunomodulating effects. Antiviral effects : INF-α, β ＞ INF-γ immunomodulating effects: INF-γ Uses: Hairy cell leukemia Multiple myeloma Malignant melanoma Hepatitis B & C Adverse reactions: Flu-like symptoms – fever, chills, headache CVS- hypotension, Arrhythmia CNS- depression, confusion

Interleukin-2 (aldesleukin, Proleukin) Proliferation of cellular immunity (Lymphocytosis, eosinophilia, release of multiple cytokines – TNF, IL-1, IFN-γ) Uses Chronic viral infections (e.g. HIV infection) Metastatic renal cell carcinoma Malignant Melanoma Toxicity Fever, Anorexia, Cardiovascular: capillary leak syndrome, Hypotension

Capillary leak syndrome (Clarkson syndrome) A rare medical condition where the number and size of the pores in the capillaries are increased which leads to a leakage of fluid from the blood to the interstitial fluid, resulting in dangerously low blood pressure (hypotension), edema and multiple organ failure due to limited perfusion.

Immunization Active – Stimulation with an Antigen Passive – Preformed antibody

Immunization Vaccines Vaccines are antigenic material derived from bacteria, viruses and specific T-cells. Which are used to modulate the immune system. Vaccines are mainly used for active Immunization. Vaccines contain an antigen as a whole killed organism, attenuated live organism or a specific protein or a peptide constituent of an organism. TYPES OF VACCINES:  BCG Vaccine (Bacillus Calmitte Guerin)  Cholera vaccine  Oral poliomyelitis vaccine  Rabies vaccine

A. Bacillus Calmette-Guerin It is the suspension of living cells of BCG strain of Mycobacterium tuberculosis. Give resistance to bacterial infections. It is also increases Humoral as well as cell mediated immune reactions. The main use of BCG is for vaccination against tuberculosis (TB). It causes activation of macrophages to make them more effective killer cells. Use: Superficial bladder cancer. Adverse Effects: Hypersensitivity, Shock, Chills

B. Cholera vaccine: It is a sterile suspension of killed strains of Vibrio cholera selected for higher antigenic property and purity. C. Oral poliomyelitis vaccine: Extensively used oral vaccine for active immunization against polio, which contain the live attenuated strains of poliomyelitis. Used for polio. D. Rabies vaccine: A sterile isotonic suspension, prepared by using strains of killed rabies virus. Used for active immunization against rabies.

Immune Globulin Passive immunization is indicated when an individual is deficient in antibodies because of genetically or acquired immunodeficiency. Passive immunization is carried out by using variety of immunoglobulins (Ig). The Ig may be either non-specific/highly specific. Which may be provided based upon the indication. The protection provided usually last from 1-3months. Ig are derived from pooled plasma of adults by an alcohol fractionation procedure. And it contains largely IgG (95%). and is indicated for Uses Antibody deficiency disorders, expose to infection such as hepatitis-A and measles, Individual is exposed to an agent, inadequate time for active immunization such as Rabies, Hepatitis B specific immunologic diseases such as immunothrombocytopinia purpura and Guillain-Barre syndrome. Immunodeficiency

Rho (D) Immune Globulin Are IgG containing a high titer of antibodies against the Rh(D)antigen on the surface of red blood cells. All donors are carefully screened to reduce the risk of transmitting infectious diseases. Mechanism of action: Acts by binding to Rho antigen, thereby preventing sensitizion. In case of Rh –ve women ma be sensitized to the foreign Rh antigen on red blood cells via the fetus at the time of birth. If women go on to have a primary immunoresponse,they will make antibodies to the Rh antigen that can cross the placenta damage subsequent fetus by lysing red blood cells.This Rh incompatibility is preventable by Rho (D)immunoglobulins. Therapeutic uses: It is a specific hyper immunoglobulin for prophylaxis against hemolytic disease o f the new born due to Rh incompatibility between mother and fetus. Antibodies against Rh(D) antigen on the surface of RBC prevent the immunological condition known as Rhesus disease (or hemolytic disease of newborn). treating chronic idiopathic thrombocytopenic purpura in Rh-positive patients who have not been splenectomized

Other Drugs: Inosiplex: Anti-viral including influenza (INFV) and parainfluenza (PIV), and herpes simplex (HSV) Azimexon: used in the treatment of melanomas Imexon: treatment of some types of cancer, including pancreatic, lung, breast, prostate, melanoma, and multiple myeloma Thymosin: ZADAXIN (synthetic thymosin alpha 1): Chronic Hepatitis B & C, Cancer Adjuvant Methylinosine monophosphate: HIV infection

Autologous Immune Enhancement Therapy The Autologous immune enhancement therapy (AIET) is an autologous immune cell based therapy wherein the patients own peripheral blood derived NK cells, Cytotoxic T Lymphocytes, and other relevant immune cells are in vitro expanded and then reinfused to tackle cancer. There are also studies proving their efficacy against Hepatitis C Viral infection and Human herpes virus 6 (HHV6) infection