Use of monoclonal antibodies in cancer immunotherapy.pptx

Use of monoclonal antibodies in cancer immunotherapy.pptx

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  Use of monoclonal antibodiesin cancer immunotherapy: types and mechanisms of action PRESENTED BY: HENSOYA A SHIMRAY BSc(H) MICROBIOLOGY SEM-V (3rd YEAR) 4512
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  Introduction • Cancer immunotherapyis one of the most innovative treatments in the current field of oncology and consists of stimulating the immune system to eliminate tumoral cells. • Monoclonal antibodies (mAbs) are glycoproteins secreted by B- cells capable of recognizing and neutralizing foreign organisms or antigens.
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  Monoclonal Antibodies • Monoclonalantibodies (mAbs) are derived from a single cell clone and can recognize a single specific region of the antigen (epitope). • Structurally, they are composed of two heavy and two light chains connected by disulfide bonds. • Monoclonal antibodies(mAbs) have shown efficacy in treating a wide range of diseases like a) Cancer b) Autoimmune disease (rheumatoid arthritis) c) Asthma
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  Use of monoclonalantibodies in cancer therapy • mAbs are commonly used in cancer therapy because of their antitumor activity by specifically interacting with tumor antigens. • Therapeutic monoclonal antibodies can be classified into four major groups according to their origin and composition . They are a) murine b) chimeric c)humanized d) fully human
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  Murine monoclonal antibodies •These antibodies are fully derived from mice (100% mouse protein). Murine mAbs are named using the prefix “-omab” at the end of the generic name. • Murine mAbs are named using the prefix “-omab” at the end of the generic name. Eg. “Afelimomab”
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  Chimeric monoclonal antibodies •Chimeric antibodies are composed of 65% of human constant regions and 25% of mouse variable region. • Chimeric mAbs are named using the suffix “-ximab” at the end of the generic name • For example, “ infliximab” is a chimeric antibody that targets Tumor Necrosis Factor-α (TNF- α) and is used to treat inflammatory diseases such as rheumatoid arthritis.
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  Humanized monoclonal antibodies •Humanized mAbs have a majority of human sequence, with only a small portion of mouse sequence in the complementary determining regions(CDRs). • They are identified by having the suffix ”-zumab”. • The main objective of humanization techniques is to increase the tolerance of the immune system for the therapeutic antibody while maintaining stability, specificity, and affinity towards the targeted antigen. • For example, “Trastuzumab” is a humanized antibody used in the treatment of HER2-positive breast cancer.
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  Fully human monoclonalantibodies • Fully human antibodies are entirely derived from human sequences, both in the constant and variable regions. • Fully human mAbs are named using the suffix “- umab” at the end of the generic name. • For example, “Adalimumab” is a fully human antibody that targets TNF- α and is used to treat various autoimmune diseases such as psoriasis.
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  Mechanisms of actionof therapeutic antibodies A) Receptor inhibition-mediated tumor cell death: This effect is stimulated by receptor agonists, like antibodies binding to tumor cell surface receptors, inducing cell death. Another mechanism of direct death occurs when antibodies bind to membrane receptors leading to cell death through the blockade of dimerization or kinase activation, altering transduction signals, which decreases proliferation and promotes apoptosis. Eg. Panitumumab B) Immune-mediated tumor cell elimination: The main objective of this mechanism is targeting and eliminating tumor cells. This type of cell death can occur by triggering one of several mechanisms, including complement-dependent cytotoxicity (CDC), antibody-dependent cell cytotoxicity (ADCC), and antibody-dependent phagocytosis
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  Figure 3. Mechanismof action of therapeutic antibodies. A: direct death. Direct tumor cell death by blockade of receptors and signalling pathways. EGFR: epidermal growth factor receptor; EGF: epidermal growth factor. B: complement dependent cytotoxicity. MAC - membrane attack complex; CD20 - CD antigen (Cluster of differentiation 20); C1q: C1q complex (complement component 1q). C: antibody-dependent cytotoxicity. FcγRIII: Receptor for IgG. D: antibody mediated phagocytosis. FcγRIII: Fc gamma receptor (FcγR).
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  Limitations of theuse of therapeutic antibodies in cancer The elevated cost and low cost- effectiveness that prevent low- income patients from accessing this type of therapy. Inability to penetrate solid tumors due to the complexity of the tumor microenvironment and the possible development of immunogenicity reactions in the host.
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  Reference • Use ofmonoclonal antibodies in cancer immunotherapy: types and mechanisms of action. Paolo Damián-Blanco et al. Bol Med Hosp Infant Mex. 2023;80(3):153-164. English. doi: 10.24875/BMHIM.23000123. PMID: 37467439.