Lecture 6- Monoclonal antibodies Flashcards Preview

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What are monoclonal antibodies?


Monoclonal antibodies are monovalent antibodies which bind to the same epitope of an antigen and are produced from a single B-lymphocyte clone


antibodies are produced by

plasma cells (mature B cells)


​which part of the antibody recongises antigen


  • Fab (fragment antigen binding) part of antibody recognises antigen
    • Hypervariable regions meaning that antibody can recognise an infinite number of antigens
      • Paratope region on antibody reacts with epitope (antibody binding site) of antigen


which part of the antibody interacts with the cell surface receptors on other cells

  • Fc (fragment crystallizable region) region
    • Interacts with cell surface receptors on other cells


Monoclonal antibodies in clinical practice


  • Diagnostics
    • E.g. immunohistochemistry (ELISA)


  • Therapeutics


Production of monoclonal antibodies


e.g. Hybridoma technology


  • First generated in mice in 1975 using a hybridoma technique
  • The generation of hybridomas involves immunising a certain species against a specific epitope on an antigen and then harvesting the B-lymphocytes from the spleen of the mouse
  • The B-lymphocytes are then fused with an immortal myeloma cell line not containing any other immunoglobulin-producing cells
  • The resulting hybridoma cells are then cultured in vitro so only the hybridomas (i.e. the fusion between the primary B-lymphocytes and myeloma cells) survive
  • Selected hybridomas are found making a specific desired clonal antibody


Types of monoclonal antibodies drugs


  • Naked monoclonal antibodies
  • Conjugated monoclonal antibodies
  • Bispecific monoclonal antibodies


Naked monoclonal antibodies

  • Derived from mice (murine)
    • Recognised as foreign- rapidly cleared and destroyed
  • Chimeric (65% human)
  • Humanised (>90% human)
  • Fully human (100% human)
    • Significant immunogenicity


Conjugated monoclonal antibodies


  • Monoclonal antibody is linked to a potent drug to allow targeted delivery to cancer cell
    • Tumour specific antigen is targeted by monoclonal antibodies
    • Drug (cytotoxic agents) internalised 9receptor mediated endocytosis)  by cancer cell and killed
      • E.g. lysosomal degradation: ADCC and induction of apoptosis
  • Limits systemic exposure
  • ADCs (antibody-drug conjugates) are designed to allow for the use of highly potent, normally intolerable, anticancer cytotoxic agents


e.g. B/T cell lymphoma


Bispecific monoclonal antibodies e.g. Mosunetuzumab


  • Utilise 2 binding domains of antibody structure
  • Bind onto 2 different cell populations--> bringing the two populations into close proximity e.g. T cell and malignant B cell (enhanced cell mediated cytotoxicity)
  • In clinical trials


How do they work in cancer?


Binding with cell surface receptors to either activate or inhibit signalling within the cell

  1. Binding with cell surface receptors to activate:
    • antibody-dependent cell-mediated cytotoxicity (ADCC) or
    • complement-dependent cytotoxicity (CDC)
  2. Internalization (ie being taken in by the cell through the membrane) for antibodies delivering toxins into the cancer cell
  3. Blocking inhibitory effects on T cells (checkpoints). Thus activating T cells to help ‘kill’ the cancer cells


Monoclonal antibodies in haemtology


  • Understanding what antigens are present on cancer cells and on normal tissue we could try to develop specific targeted treatments.
  • Cluster of differentiation (CD) classification.


What type of cancer is lymphoma?


  • Lymphoma divided into B and T cell neoplasms – clonal proliferations of lymphoid cells
  • It typically causes enlargement of lymph nodes
  • The spleen, bone marrow and other areas of the body such as liver, skin, testes and bowel (‘extra-nodal’) may also be involved


People with lymphoma often complain of



  • drenching night sweats
  • fevers
  • weight loss .. But some have none of these symptoms


lymphoma b cells express

CD20 - therefore creation of mAb which binds to CD20 e.g. Rituximab 


types of B cell lymphoma

  • follicular lymphoma
  • diffuse large B cell lymphoma


clinical examples of lymohoma


Lymphoma treatment


  • Chemotherapy
  • Radiotherapy
  • Monoclonal antibody therapy
  • Emerging new targeted therapy
  • Stem cell transplantation


mAbs in Lymphoma


Side effects of monoclonal antibodies in treatment of lymphoma


  • Some have no or mild symptoms eg mild fatigue
  • Many have a mild reaction to the 1st infusion and then tolerate subsequent treatments well
  • A few people will have severe infusion related reactions as their immune system reacts to the presence of a ’foreign’ protein


monoclonal antibodies in solid cancer


monoclonal antibodies in autoimmune disease


monoclonal antibodies in cardiology 


monoclonal antibodies in endocrine disorders