Immunotherapy

Question 1

COX 2 inhibitors

Answer 1

inhibit the action of COX2 which is only present in inflamed tissue (indirectly affect NF-kB signalling)
- reduces prostaglandin synthesis
(prostaglandin E2/D2 = vasodilation = increased immune infiltration and swelling)
- side effects: gastric ulcers, bleeding, kidney issues, but less than NSAIDs and only after long term use

Question 2

TNF inhibitors

Answer 2

biologics (humanised antibodies/chimeric antibodies)
- bind TNF to reduce effect on receptor
- immune suppression
- side effects: anaphylaxis, heart failure, bone marrow depletion

Question 3

soluble IL-6

Answer 3

humanised antibody/chimeric receptor / nanobody
- acts to decrease IL-6, decreasing effect on IL-6 receptors on T and B cells
- liver damage, gut perforation, increased fungal/bacterial infections

Question 4

IFNa/R1 inhibitors

Answer 4

humanised antibody/chimeric receptor
- prevent receptor activation
- prevents communication between DCs and adaptive immune response
- latent virus activation and respiratory infection

Question 5

IL-12/23 inhibitors

Answer 5

humanised antibody/chimeric receptor that binds to p40 subunit of IL-12/23
- decreased T cell proliferation
- decreased inflammation
- latent virus activation and respiratory infection

Question 6

CTLA4-Fc fusion

Answer 6

binds to CD80/86 on DC’s to prevent T cell activation
- decrease adaptive response
- cytokine-activated T cells remain = allows baseline immune response
- distributed in lymph and blood
- lasts 4-6 weeks
- risk of anaphylaxis, latent virus activation and respiratory infection

Question 6

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Question 7

calcineurin inhibitors

Answer 7

result in decreased transcription of IL-2
- decreased T cell proliferation
- increased risk of skin cancer, bone marrow depletion, kidney impairment, decreased healing

Question 8

IL-2 receptor inhibitors

Answer 8

humanised antibody/chimeric receptor that binds to IL-2 to inhibit
- T cell specific
- decrease T cell proliferation, maintaining baseline level
- latent virus activation and respiratory infection

Question 9

nucleotide synthesis inhibitors

Answer 9

non-specific inhibitors of nucleotide synthesis, act in rapidly dividing cells
- damage to gut, kidney, fetal development, endocrine system, bone marrow, healing and homeostatic responses

Question 10

BCR inhibitors

Answer 10

humanised antibody/chimeric receptor bind to BCR
- complete B cell depletion, induce cytokine storm, increase immune response.
- 15% chance of death via acute or pulmonary toxicity

Question 11

integrin inhibitors

Answer 11

humanised antibody/chimeric receptor that target a4b7/a4 integrins that are specific to T and B cells
(integrins are upregulated on activated T/B cells)
- prevents binding to MAdCAM
- prevents diapedesis
- allows baseline T/B cell signalling
- protection without overactivation
- latent virus activation and respiratory infection

Question 12

Jakinibs

Answer 12

mimic action of SOCS; bind to JAK to prevent phosphorylation
- prevents downstream signalling on T cells and B cells
- can be specific
- side effects linked to specific JAK targeted
- topical/injection reduce side effects