2. Therapeutic Antibodies Flashcards

1
Q

Mechanisms of Monoclonal Antibody Induced Cytotoxicity

[Looking for 5 mechanisms]

A
  1. Recruitment of human immune function
    - ADCC, Phagocytosis, Complement-mediated lysis
  2. Direct cytotoxic or down-regulatory effect of mAbs
    - Blockade of growth factor receptors
    - Induction of apoptosis
  3. Delivery of cytotoxic conjugate via mAbs
    - Chemotherapeutic drug, conjugation to a mAb ensures targeted delivery
    - Enzyme-prodrug activation (ADEPT). enzyme attached to mAb, mAb attaches to tumour cell, therefore prodrug converted to drug by enzyme only in presence of tumour cell.
  4. Indirect induction of immune response to tumour via stimulation of the host cellular response
  5. Bispecific antibodies (have specificity for 2 different antigens) cross-link target cells and cytotoxic effector cells, enabling ADCC, phagocytosis etc.
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2
Q

Clinical Uses of Monoclonal Antibodies

[Looking for 3 uses]

A
  1. Diagnostic imaging and therapy of cancer
  2. Treatment of infections
  3. Induction of immunosuppression
    - Treat autoimmune and inflammatory diseases
    - Prevent graft rejection in transplantation
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3
Q

Examples of therapeutic monoclonal antibodies:

[Give 3 examples]

A
  • Rituximab, treats Non-Hodgkin’s Lymphoma and Rheumatoid Arthritis
  • Herceptin, treats patients with metastatic breast cancer
  • Cetuximab, binds to EGF receptor and treats metastatic colorectal cancer
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4
Q

Immune checkpoint blockade by monoclonal antibodies:

A

Immune checkpoints in the immune system either “turn up” a signal; (co-stimulatory molecules) or “turn down” a signal

Directing mAbs against key immune checkpoints shows huge promise in cancer treatment

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5
Q

Infliximab

A
  • A mAb used to treat rheumatoid arthritis, Crohn’s disease, psoriasis
  • Chimeric human IgG1
  • Binds to human tumour necrosis factor α (TNFα)
  • Blocks the ability of TNFα to induce:
    1. Pro-inflammatory cytokines IL-1 and IL-6
    2. Increased leukocyte migration
    3. Increased neutrophil and eosinophil activity
    4. Acute phase proteins
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