Block 3 Lecture 3 -- Vaccines and Immunotherapy Flashcards
How do CTLs kill?
1) granzyme and perforin
2) FasL/Fas
Where is FasL and where is its ligand?
FasL located on CTL
Fas = CD95 on tumor
What are the results of FasL/Fas binding?
caspase activation
What is required for both methods of CTL killing?
CD8/TCR + pMHC-I
What are ways to evade the immune response?
1) low immunogenicity
2) tumor treated as self-antigen
3) antigenic modulation
4) tumor-induced immune suppression
5) tumor-induced privileged site
6) immuno-editing
What is an adjuvant?
substance added to or emulsified with antigen capable of increasing Ab or T cell production to the antigen
What are the requirements for an antigen used in a vaccine?
1) able to induce clonal B/T cell differentiation and proliferation
2) induce memory response
What adjuvant is approved in the US?
alum (aluminum hydroxide/phosphate) formulations
How does alum as an adjuvant work?
1) depot to trap antigen at injection site
2) continued stimulation of immune system (more APCs recruited)
- - other adjuvants may direct pMHC presentation
When are adjuvants usually used?
for toxin-vaccines
– bacterial/viral components may not need adjuvant
What is Provenge?
autologous cellular immunotherapy
– DCs loaded with Ag ready to activate T cells
When is Provenge due?
for asymptomatic or minimally asymptomatic metastatic castrate-resistant prostate cancer
What are the 3 functions of mAbs in cancer?
1) can target immune system to destroy tumor cells
2) can inhibit cell signaling/proliferation
3) can carry conjugated drugs/radiolabel
What are the advantages of cancer immunotherapy?
1) durable response
2) slows tumor growth
3) relatively non-toxic
What are the disadvantages of cancer immunotherapy?
1) low response rate
2) altered pattern of response (delayed)
3) autoimmune-related adverse effects
What are the 2 main interactions in the immunosynapse?
1) pMHC + TCR
2) B7 (APC) + CD28
How can the pMHC + TCR synapse be improved?
1) vaccines
2) stimulation of DCs with antigens
- - provenge
How can the B7 / CD28 interaction be improved?
1) increased B7-1/2 expression
- - modified cell lines (drug delivery is a problem)
2) blocking CTLA4
- - ipilimumab
- - tremulimumab
What other signal is important in the immune synapse?
PDL1 (APC/tumor) - PD1
– PD1 is inducible, expressed on tired T cells
What is the PD1 inhibitor?
Nivolumab
What is the function of IL-2?
immune cell growth and division
How are cancer immunotherapies characterized?
1) non-specific vs. specific
2) passive vs. active
What does CAR-T stand for?
chimeric antigen receptor T cell therapy
How are CAR-T cells made?
1) T cells removed
2) modified with virus to tumor-specific receptor composed of multiple fragments
3) population expanded in vitro
What is the goal of CAR-T cell therapy?
1) want CAR-T cells to recognize Ag
2) want CAR-T cels to expand in vitro
What are examples of non-specific immunotherapy?
1) CAR-T
2) cytokines
3) mAbs