JT- Cancer (CD20) Autoimmunity (TNF-a) Dementia (Amyloid)

Question 1

What are the main targets for antibodies in cancer therapy? (2)

Answer 1

• Cell surface proteins (e.g., CD20, CD52)
• Antibodies engage Fc receptors on immune cells to kill via cytotoxicity or phagocytosis

Question 2

What are two examples of antibodies used in cancer therapy? (2)

Answer 2

• Rituximab → targets CD20
• Alemtuzumab → targets CD52

Question 3

How do antibodies induce cell signaling?

Answer 3

By crosslinking antigens, they can mimic ligand signaling and trigger cytotoxicity

Question 4

How do antibodies interact with the tumor microenvironment? (1)

Answer 4

They modify the environment so the immune system can recognize and attack tumor cells
(e.g., PD-1 inhibitors)

Question 5

What is Rituximab and what does it target? (4)

Answer 5

• First FDA-approved antibody for cancer
• Chimeric monoclonal antibody
• Binds CD20 on B cells
• Used to treat B cell lymphoma

Question 6

What makes CD20 a suitable antibody target? (3)

Answer 6

• Small membrane protein with 2 external loops
• Knockout causes no harmful effects
• Extracellular loop is critical for therapeutic binding

Question 7

What happens when CD20 is crosslinked by anti-CD20 antibodies? (3)

Answer 7

• CD20 is recruited into lipid rafts
• Enables C1q binding → activates complement system
• Enhances binding to Fc receptors

Question 8

Why are Fc receptors (FcRs) essential for antibody therapy? (2)

Answer 8

• Enable immune-mediated killing
• Rituximab is ineffective without FcR engagement

Question 9

What are the mechanisms of Rituximab action? (3)

Answer 9

• Complement-dependent cytotoxicity (CDC)
• ADCC (Antibody-dependent cellular cytotoxicity)
• Phagocytosis via FcR+ immune cells

Question 10

What are causes of resistance to Rituximab? (4)

Answer 10

• Loss of CD20 expression
• Resistance to CDC, ADCC, apoptosis
• Influence of tumor microenvironment
• Trogocytosis leads to CD20 internalization

Question 11

How does antibody binding influence function? (3)

Answer 11

• Rituximab binds between CD20 clusters and activates FcγRIIB, which internalizes CD20
• FcγRIIB provides inhibitory signals
• Type II antibodies avoid FcγRIIB activation → reduce CD20 internalization

Question 12

How does CD27 stimulation enhance mAb therapy? (4)

Answer 12

• Activates T and NK cells
• Increases chemokine and IFNγ production
• Promotes myeloid activation and infiltration
• Enhances macrophage-mediated phagocytosis

Question 13

What effects does TNF-α have in rheumatoid arthritis? (4)

Answer 13

• Activates endothelial cells to express adhesion molecules
• Recruits immune cells
• Stimulates** osteoclasts and fibroblasts**
• Contributes to** cartilage degradation**

Question 14

How is rheumatoid arthritis different from osteoarthritis? (2)

Answer 14

• RA: Autoimmune and inflammatory joint disease
• OA: Mechanical wear-and-tear → cartilage loss

Question 15

What is Etanercept and how does it function? (3)

Answer 15

• Fusion protein: TNF receptor + IgG1 Fc
• Improves half-life
• Targets TNF-α, mimicking antibody activity

Question 16

What are the risks of using TNF-blocking therapies? (4)

Answer 16

• TNF is essential for dendritic cell maturation
• Needed for host defense against TB, fungi, Listeria
• Plays a protective role in autoimmunity (e.g., lupus, MS)
• TNF blockers are not recommended for MS