2. Therapeutic Antibodies Flashcards
1
Q
Mechanisms of Monoclonal Antibody Induced Cytotoxicity
[Looking for 5 mechanisms]
A
- Recruitment of human immune function
- ADCC, Phagocytosis, Complement-mediated lysis - Direct cytotoxic or down-regulatory effect of mAbs
- Blockade of growth factor receptors
- Induction of apoptosis - 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. - Indirect induction of immune response to tumour via stimulation of the host cellular response
- Bispecific antibodies (have specificity for 2 different antigens) cross-link target cells and cytotoxic effector cells, enabling ADCC, phagocytosis etc.
2
Q
Clinical Uses of Monoclonal Antibodies
[Looking for 3 uses]
A
- Diagnostic imaging and therapy of cancer
- Treatment of infections
- Induction of immunosuppression
- Treat autoimmune and inflammatory diseases
- Prevent graft rejection in transplantation
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
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
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