Biologics PDF

Biologics Created @October 24, 2024 5:20 PM Class Pharmacology 1A Course PHPH10003_Biologics_lecture 2_ZJP BB(1) Materials (1).pdf PHPH10003_Biologics_lecture 1_ZJP (1).pdf Files &...

Biologics Created @October 24, 2024 5:20 PM Class Pharmacology 1A Course PHPH10003_Biologics_lecture 2_ZJP BB(1) Materials (1).pdf PHPH10003_Biologics_lecture 1_ZJP (1).pdf Files & https://www.nature.com/articles/nrd.2016.21 media Files & https://journals.sagepub.com/doi/10.3821/1913-701X-143.3.134 media 1 BIOLOGICS - Can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances May be living entities such as cells and tissues A wide range of products vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins FDA definition Biologics 1  Medical and therapeutic uses insulin production monoclonal antibodies vaccines industrial use biotechnology used to study function of specific proteins by producing them in large quantities Biologics 2  Common features of biologics produced by extracellular injectable living cells targets a structure depends on not available extracellular living cells via oral route targets used for production may linger in highly specific the body for most are too long periods of large to cross time cell membrane Types of biologics monoclonal antibodies proteins viral and non viral vectors oligonucleotides are short sequences of dna Biologics 3  cells i.e stem cells ○ Ligand blockade: The therapeutic antibody binds to the endogenous ligand, preventing it from binding to the receptor. ○ Receptor blockade: The therapeutic antibody binds to the receptor, preventing the endogenous ligand from binding. Biologics 4  ○ Receptor downregulation: The therapeutic antibody binds to the receptor, causing it to be internalized and degraded. ○ Signalling induction: The therapeutic antibody binds to the receptor, triggering a signalling cascade that leads to a desired cellular response. ○ Cell depletion: The therapeutic antibody binds to a cell surface antigen, leading to the destruction of the cell through complement- dependent cytotoxicity (CDC), antibody- dependent cytotoxicity (ADCC), or antibody- dependent phagocytosis (ADCP). Biologics 5  Complement- dependent cytotoxicity - mAb binds to antigen on surface on the surface of a tumour cell, it can activate the complement system. c1 complex of the complement binds to ANTIBODY Fc region. activation leads to membrane attack complex being formed which creates pores in the tumour cell membrane, leading to cell lysis and death Antibody-dependent cell mediated cytotoxicity mAb binds to antigen Natural killer cells recognise the antibody coated cell thru Fcy receptors on NK cells surface when Nk is activated, releases cytotoxic granules i.e > perforins and granzymes that induce apoptosis Antibody- dependent cellular phagocytosis mAb binds.. macrophages recognize antibody-coated tumour cells thru Fcy receptors macrophage engulf (phagocytosis) antibody coated cell when inside the macrophage, tumour cell is degraded by lysosomal enzymes Biologics 6  ○ Payload delivery: The therapeutic antibody is conjugated to a cytotoxic agent, radioactive ligand, or other payload, which is delivered specifically to the target cell what diseases could be treated my Monoclonal antibodies auto-immune diseases cancer inflammatory diseases Role of TNF-a in arthritis TNF-a is a cytokine and the overproduction of it , is involved in the development of rheumatoid arthritis various cell types within the joint i.e macrophages, t-cells,neurons,muscle cells can Biologics 7  produce TNF-a TNF-a exists in as a transmembrane protein and in a soluble form Both forms of TNF-α can bind to TNF receptors on target cells. This binding triggers a cascade of downstream effects, including: Proliferation: TNF-α stimulates the proliferation of synovial fibroblasts, contributing to the formation of the pannus, a thickened layer of inflamed tissue that damages the joint [not in sources]. Cytokine production: TNF-α induces the production of other pro-inflammatory cytokines, amplifying the inflammatory response. Antibody production: TNF-α can stimulate the production of antibodies, which may contribute to the autoimmune response in rheumatoid arthritis [not in sources]. Apoptosis: TNF-α can induce apoptosis (programmed cell death) in certain cells, leading to joint damage [not in sources]. Infiltration: TNF-α promotes the infiltration of immune cells into the joint, further contributing to inflammation. Angiogenesis: TNF-α stimulates the formation of new blood vessels, providing nutrients and oxygen to the inflamed tissue and supporting the growth of the pannus [not in sources]. Biologics 8  FAST acting insulin analogues long acting insulin analogues meal control basal control quicker absorption slow release fast acting long lasting (42hrs) combination therapy safer - hypoglycaemia insulin aspart produced in yeast flexible dosing insulin degludec produced in yeast insulin lispro produced in bacteria Biologics 9  Stable Transfection Transient transfection DNA inserted into host cell genome DNA or mRNA put in the cytosol but does not Biologics 10  integrate into the genome DNA passed into daughter cells during expression og gene is temporaryn as DNA does cell divisom, meaning expression of not become a permanent part of cells genetic transgene is permanent material.it will be degraded long term short term Biologics 11 Biologics 12 Biologics 13 Biologics 14  Antisense oligonucleotides Short DNA or RNA molecules (at least 15-mer) Complementary to part of a gene or gene product Supress expression of a harmful gene Enzyme-resistant Do not reach central nervous system Biologics 15