IMMUNOTHERAPY ppt

April 2, 2018 | Author: Pandiya Raja | Category: Immune System, Antibody, Antigen, Cancer, Medicine


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CONTENT  DEFENITION  TYPES OF IMMUNOTHERAPY  CYTOKINES  CANCER VACCINES  MONOCLONAL ANTIBODIES  CYTOKINES INHIBITORS  IV IMMUNOGLOBULINS  IMMUNOSUPRESSENTS TYPES Active immunotherapy Passive immunotherapy Active immunotherapy It is the type of immunotherapy that attempts to stiumlate the host intrensic immune response to a disease  Specific active immunotherapy  Non specific active immunotherapy Specific active immunotherapy The generation of cellmediated and antibody immune responses focused on specific antegen. Eg.cancer vaccines Non specific immunotherapy the generation of general immune system response using cytokines Specific active immunotherapy  Cancer vaccines  Cellular therapies  adjuvants . . Cancer vaccines cancer vaccines are active immunotherapy because they meant to triger the patient immune system to respond.part of the cell. cancer vaccines may contain cancer cells .or purified tumor specific antigen.  Two catogories of cancer vaccine  cell based in which the patient cancer cell is cultured with patients own immune system cells and derived back to the same patient.. .  Vector based in which the engineered virus or oter vector is used to inntroduce cancer specific proteins and other molecule in order to stimulate the patient immune system to recoganise the tumor cells to fight the cancer. colorectal cancer.ovarian breast cancer  Antigen vaccines-prostate.  Dentritic cell vaccine  DNA vaccines  Vector based vaccines .Examples  Tumor cell vaccines-kidney.  Cellular therapies these are single type agent derived from the cancer patients which are modified in the labouratry to become more adapt at recognising and killing the tumor cells this type of immunotherapy is designed to boost specific part of immune system to cause tumor cell death Vaccines in contrast attempts to get the body immune system rect to specific antigen Eg.lympocyte activated killer cell therapy . cancer vaccines increases or boost the immune response to the particular system. Adjuvant immunotherapy an adjuvant is an any material which when injected together with an antigenic protein or other substance like monoclonal antbodies. BCG vaccine . Eg. IL2 promote T-cell and NK cell growth .IL-6  Indirect enhancement of antitumor response Eg.Non specific active immunotherapy  Cytokines destruction of tumor cell by two mechanism  direct antitumor eg.TNF alpha.  Cytokine based therapy IL-2 IFN alpha GM-CSF metastatic melanoma RCC malignant melanoma hairy cell lukemia kaposis sarcoma lukemia Bone marrow /stem cell transplant chrons disease . . BCG therapy BCG as a treatment of choice in early form of bladder cancer exact mechanism not known activates both macrophage and lymphocytes  Cell therapy the transfer of live .whole cells into the patient can also be used to achive non specific immunotherapy aginst cancer. when this combination of IL2 & LAK given to patient with advanced metastatic melanoma and RCC complete tumour regression can be achieved in 10 % of cases. . Example  In metastatic melanoma patients.human pheripheral blood mononuclear cells(PBMCs) can be isolated and fed with IL-2 to generate class of cells called lymphokine activated cells(LAK). It do not stimulate a patient immune system to actively respond to a disease in the way vaccines does . Passive immunotherapy this comprised of antibodies and other immune system component that are made ouside the body and administerd to the patient to provide immunity against the disease.  Monoclonal antibodies thearapy  Cytokine inhibitors  Tolerance induction  IV immunoglobulin  Immuno supressants  Haemopoitic stem cell transplantation . gemtuzumab Radiolabelled antibodies eg. cetuximab. eg . monoclonal antibody therapy  Types Naked monoclonal antibodies.tositumomab Chemolabelled antibodies eg.trastuzumab Conjugated monoclonal antibodies antibodies contain immunotoxin eg.brentuximab . . . infliximab Specific receptor can be blocked eg.etanercept Intracellular process which produce the active protien can be inhibited Cytokines can be neutralized in the circulation eg. CYTOKINES INHIBITOR     these are cytokine specific substance that inhibit the biological actvities of specific cytokines in anumber of diffirent ways Production can be blocked eg.kineret . antibodies Mechanism of action uses kineret IL alpha antagonist Rheumatoid arthrites Sepsis osteoarthrites Ulcerative colitis Ankylosing spondylites Chrons disease Rheumatoid arthrites Psoriatic arthrites Ankylosing spondylites infliximab TNF alpha antagonistic enarcept TNF alpha antagonistic . Immune thrombocytopenia  Acute infections. .  Autoimmune diseases e.g.IV immunoglobulins  It contains the pooled IgG extracted from the plasma of over one thousand blood donors.  IVIG's effects last between 2 weeks and 3 months.  It is mainly used as treatment in three major categories:  Immune deficiencies . . IVIG dose  Dosage of IVIG is dependent on indication.  For primary immune dysfunction 100 to 400 mg/kg of body weight every 3 to 4 weeks is implemented.  For neurological and autoimmune diseases 2 grams per kilogram of body weight is implemented for three to six months over a five day course once a month. Then maintenance therapy of 100 to 400 mg/kg of body weight every 3 to 4 weeks follows. Mechanism of action.  Blockade of Fc receptors mononuclear or polynuclear phagocytes  Inhibition of complement consumption by pathogenic antibodies  Interference with T cell regulation and cytokine release  Feedback inhibition of autoantibody synthesis by auto reactive B cells . FDA-approved indications  Allogeneic bone marrow transplant  Chronic lymphocytic leukemia  Idiopathic thrombocytopenic purpura  Pediatric HIV  Primary immunodeficiencies  Kawasaki disease  Kidney transplant with a high antibody recipient or with an ABO incompatible donor . immunosupressents  Glucocorticoids  Calcineurin inhibitors  Cyclosporine  Tacrolimus  Antiproliferative / antimetabolic agents  Sirolimus  Everolimus  Azathioprine  Mycophenolate Mofetil  Others – methotrexate. thalidomide and chlorambucil . cyclophosphamide.  Antibodies  Antithymocyte globulin  Anti CD3 monoclonal antibody  Muromonab Daclizumab. etanercept . basiliximab  Anti IL-2 receptor antibody –   Anti TNF alpha – infliximab. Immunosuppressants  Organ transplantation  Autoimmune diseases Problem Life long use Infection. cancers Nephrotoxicity Diabetogenic . Monocytes display poor chemotaxis  Broad anti-inflammatory effects on multiple components of cellular immunity .glucocorticoids  Induce redistribution of lymphocytes – decrease in peripheral blood lymphocyte counts  Intracellular receptors – regulate gene transcription  Down regulation of IL-1. IL-6  Inhibition of T cell proliferation  Neutrophils. Uses of glucocorticoids  Transplant rejection  GVH – BM transplantation  Autoimmune diseases – RA. Hematological conditions  Psoriasis  Inflammatory Bowel Disease. SLE. Eye conditions . toxicity  Growth retardation  Avascular Necrosis of Bone  Risk of Infection  Poor wound healing  Cataract  Hyperglycemia  Hypertension . Calcineurin inhibitors  Cyclosporine  Tacrolimus  Most effective immunosuppressive drugs  Target intracellular signaling pathways  Blocks Induction of cytokine genes . . uveitis  Psoriasis  Aplastic anemia  Skin Conditions. Alopecia Areata.Cyclosporine  More effective against T-cell dependent immune mechanisms – transplant rejection. Pemphigus vulgaris. IBD.Atopic dermatitis. Lichen planus. Pyoderma gangrenosum . Liver. Oral Uses  Organ transplantation: Kidney. autoimmunity  IV. Heart  Rheumatoid arthritis. Toxicity : Cyclosporine  Renal dysfunction  Tremor  Hirsuitism  Hypertension  Hyperlipidemia  Gum hyperplasia  Hyperuricemia – worsens gout  Calcineurin inhibitors + Glucocorticoids = Diabetogenic . Tacrolimus  Inhibits T-cell activation by inhibiting calcineurin  Use  Prophylaxis of solid-organ allograft rejection . infections .Tacrolimus  Nephrotoxicity  Neurotoxicity-Tremor.Toxicity . headache. motor disturbances. seizures  GI Complaints  Hypertension  Hyperglycemia  Risk of tumors. Antiproliferative and Antimetabolic drugs      Sirolimus Everolimus Azathioprine Mycophenolate Mofetil Others:  Methotrexate  Cyclophosphamide  Thalidomide  Chlorambucil . Sirolimus  Inhibits T-cell activation and Proliferation  Complexes with an immunophilin. Inhibits a key enzyme in cell cycle progression – mammalian target of rapamycin (mTOR) . tumors  Drug Interactions: CYP 3A4 .Sirolimus Uses  Prophylaxis of organ transplant rejection along with other drugs Toxicity  Increase in serum cholesterol. Triglycerides  Anemia  Thrombocytopenia  Hypokalemia  Fever  GI effects  Risk of infection. Everolimus  Shorter half life compared to sirolimus  Shorter time taken to reach steady state  Similar toxicity. drug interactions . Azathioprine  Purine antimetabolite  Incorporation of false nucleotide 6 Thio-IMP 6Thio-GMP 6Thio-GTP  Inhibition of cell proliferation  Impairment of lymphocyte function Uses  Prevention of organ transplant rejection  Rheumatoid arthritis .     thrombocytopenia.Toxicity .Azathioprine  Bone marrow suppression. anemia Increased susceptibility to infection Hepatotoxicity Alopecia GI toxicity .leukopenia. Antibodies  Against lymphocyte cellsurface antigens  Polyclonal / Monoclonal . Anti-thymocyte Globulin  Purified gamma globulin from serum of rabbits immunized with human thymocytes  Cytotoxic to lymphocytes & block lymphocyte function Uses  Induction of immunosuppression – transplantation  Treatment of acute transplant rejection Toxicity  Hypersensitivity  Risk of infection. Malignancy . Anti-CD3 Monoclonal Antibody  Muromonab-CD3  Binds to CD3. a component of T-cell receptor complex involved in  antigen recognition  cell signaling & proliferation . Muromonab-CD3 Antibody treatment Rapid internalization of T-cell receptor Prevents subsequent antigen recognition . Chills. Headache. weakness .Uses  Treatment of acute organ transplant rejection Toxicity  “Cytokine release syndrome”  High fever. Tremor. myalgia. arthralgia. monocytes.Campath-1H (Alemtuzumab)  Targets CD52 – expressed on lymphocytes. Macrophages  Extensive lympholysis – Prolonged T & B cell depletion Uses  Renal transplantation .
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