Biological Molecules Study Notes

What is a biological? A drug which is extracted from a biological source. what can biologicals be •(recombinant) proteins, nucleic acids or living cells what are recombinant proteins •Proteins isolated from tissue or produced in vitro can be used as drugs when injected What is the mechanism of action of re- - Substitute function of protein that is not combinant proteins there or not functioning well example of recombinant proteins •Insulin •Erythropoietin •Blood factors •Interferons •Growth Factors what is insulin •Produced by beta cells in the Islets of Langerhans in the Pancreas • •Hormone that regulates blood glucose levels Pros of recombinant insulin •Increased purity •Decreased chance of an immune response •Less expensive •Easy to introduce favourable mutations in recombinant proteins. •Lispro (Humalog) does not dimerise, more easily absorbed -> Fast acting examples of modified insulin analogue •Glargine (Lantus) forms aggregates -> long acting what cause haemophilia X-linked recessive mutations in Factor VIII or IX what is the con of recombinant biologics contamination 1/6 when and what produces antibodies •Antibodies produced as part of the adaptive immune response •Variable domain specifically binds to foreign molecules (antigen) •Produced by B lymphocyte (B cell) •Each B cell produces an antibody with different antigen binding domain •When B cells encounter antigen it will produce soluble antibodies •Blocking: Anti-TNF-alpha (adalimumab) •Receptor antagonist: Anti-HER2 •Targeting: Toxin/radiation for a specific cell, as it transports the toxin/radioactive material to the target cell •Compliment-dependent cytotoxicity: are part of the innate immune systems and form a complex that makes holes in the Give the many possible mechanisms of cell membrane •Antibody: marks the cell for the effector actions of biological antibodies. (5 cell to come and destroy it, such as NK cells and monocytes .•Agonist 2/6 1. There is the induction of an antigen into a mouse. 2. Then there is the production of B-cells which can produce the specific antibodies against the antigen. 3. The B-cells are fused with the myeloDescribe the development of monoclon- ma cells to form hybridoma cells to produce the wanted antibody at a wide al antibodies scale. 4. Therefore, there is the production of the antibody. Recombinant DNA technology of mouse antibodies how are Ximab + Zumab drugs produced genetically modified mouse that produces human antibodies How are Umab drugs produced Describe the different applications of next generation antibodies. (5) •Antibody drug conjugates •Improved delivery strategies •Glycoengineered antibodies •Antibody fragments: removal of the constant domain to remove the chance of immune recognition 3/6 •Bispecifics: each arm binds to a different target, such as an antigen and a T-cell. •Bone marrow transplantation •Stem cell therapy •CAR T cells What are the 3 different cellular therapies n How do bone marrow transplantations work transfer of haematopoietic stems cells to treat blood cancers (Leukaemia, Lymphoma, Myeloma) and other blood disorders (anemia) •Patient's own cells (autologous) or donor-derived (allogenic) 1. Remove blood form the patient to obtain the T-cells 2. Make CAR T cells in the lab by adding antigen receptors on the cell surface on the T cells , which are complementary to cancer cell antigens. Describe how CAR T cells are produced 3. Grow millions of these CAR T cells 4. Infuse the CAR T cells into the patient, to kill cancer. so complimentary action will destroy the cancer. •Addition of a kill switch if the CAR T cell do not go to plan What is altered in the allogenic CAR T •Addition of a cancer-recognising recepcell before transfusion for cancer treattor ment? (3) •Remove CD52 receptors and TCRs to prevent host vs Graft disease. 4/6 •Highly specific, less off-target effects •Well-tolerated (as they look just like endogenous proteins) what are the advantages of biologicals •Can perform functions that cannot be mimicked with small molecules •Replace proteins •Specifically activate immune cells •Biologicals are enormous compared too small molecules (Poor absorption in gut, Need to be injected) •Biologicals more complex (May be a mixture, Multiple functional what are the disadvantages of biologidomains) cals •Can only target extracellular protein/molecule •Production via mammalian cells is a laborious and slow process (Costly, Small scale of production (few kg/year)) •Shorter shelf-life •Short for insulin •Very long for therapeutic antibodies •Unquantifiable for cellular therapies biologicals have variable half life; give exmaples what is clearance done by for biologicals •by intracellular lysosomal degradation The proteins and the cells of the patient: What does the efficacy of biologicals de- •Complement/Immune cells pend on? •Anti-drug antibodies •Patient T cells may be less functional •Safe: Less toxicity, and no drug-drug inGive two reasons why biologicals are teractions safe, and one about why they are not. •Unsafe: Increased chance of allergic reactions occuring. 5/6 •Hard to generate products that are all the same, as they are produced by cells •Not all the components of the molecule Why do biologicals have a different regis known ulatory status? (4) •Production process is the same every time, but the product isn't. •Biosimilars 6/6