Lecture 13 - Immunotherapy Flashcards
Define immunotherapy
biological treatment of disease by activating or suppressing the immune system
Active Immunotherapy
generated by the body in response to stimuli
Passive Immunotherapy
donated or laboratory made immune system components administered to body
How do we know that the immune system fights some forms of cancer?
- tumor-specific CD8+ T cells found in tumors
- Mononuclear infiltrates into masses
- Increased incidence in immunosuppressed patients
- cancer remissions following immunomodulator tx
Why are canine cutaneous histiocytoma considered a surgical emergency
they quickly regress due to CD4+/CD8+ T cell infiltration
Tumor-associated antigen (TAA)
normal proteins overexpressed by tumor cells
Tumor-specific antigen (TSA)
expressed by tumor cells but not present in normal host cells
Why is active immunotherapy against TAA tricky
the proteins are expressed on both normal and cancer cells so tx can be prevented by tolerance of self-reactive B and T cells
how would passive immunotherapy target TAAs
antibodies that target the antigens via injection
CD20
high expression on B cell lymphomas
normally expressed on B cells
not expressed on antibody-producing cells
How does Rituximab (anti-CD20) work
binds to CD20 and kills expressing cells
what is a downside to the use of Rituximab (anti-CD20)
depletion of memory B cells
What are two considerations when translating the use of monoclonal cancer antibody tx to vet med
- mAbs need to bind tightly to antigen
- Fc portion needs to be functional
What are TSAs presented by
MHC on tumor cells
What do TSAs arise from
genetic mutations or viral infections
T/F: TSAs would be easier to target than TAAs because they are different from host cell proteins
True
What is TSA active immunotherapy
vaccines
What is TSA passive immunotherapy
adoptive cell therapy with T cells
CAR-T
Chimeric antigen receptor T cell
Summarize CAR-T construction
- isolate T cells from patient
- identify target antigen on neoplastic cells
- create variable fragment against antigen
- incorporate into T cell genome vi retrovirus
T/F: CAR-T is MHC-restricted
False
What do CAR-T mainly target in practice
lymphoma
what is a potential side effect of CAR-T
cytokine release syndrome/SIRS because of the release of inflammatory cytokine and macrophage activation
What is upregulated in dogs with atopic dermatitis
IL-31
what hypersensitivity does atopic dermatitis fall under
type 1
what is required for hypersensitivity reaction in AD
initial exposure and production of IgE, re-exposure where IgE binds to mast cells and the cross-link releases histamines
What is the active AD immunotherapy target
TH2/IgE
*going after large complexes
What is the passive AD immunotherapy target
prevention of TH2 cytokine symtoms
Allergen-specific immunotherapy (ASIT)
low dose of allergens to promote tolerance (IL-10 secretion, decrease in IgE)
How does apoquel work
acts as a JAK1 inhibitor (prevents intracellular signaling after cytokine binding)
How does cytopoint work
monoclonal antibody neutralizing IL-31
What are 3 stressful situations in an animal’s life
- weaning
- transport
- sickness
Metaphylaxis
treatment of animals to reduce infectious disease even though they are not currently sick
How do PRRs stimulate the immune system
increase circulating cytokines
Define cancer
uncontrolled growth of progeny of transformed cells (morphological, biochemical, growth)
Define benign
expansile, compress surrounding tissue
Define malignant
invasive, metastasize
