Lecture 5 Flashcards
Lymphoma presents as a
solid tumour of lymphoid cells
Hodgkin’s lymphoma: involves the presense of a type of cell called the
Reed-Sternberg cell.
Myeloma/multiple myeloma is a
What is it normally preceded by..
cancer of plasma cells
preceeded by an asymptomatic, premalignant stage of clonal plasma cell proliferation (called MGUS)
A common pathlogy of B cell cancers is a crowding of ______ cells, which limtits the function of normal haemopoetic cells such as RBC and WBC that are essential
therefore you get:
A common pathlogy of B cell cancers is a crowding of malignant cells, which limtits the function of normal haemopoetic cells such as RBC and WBC that are essential
therefore you get:
infection
bleeding problems
respiratory failure
Myeloma cels bind to ____ cells in the bone marrow
stromal (connective tissue cells of any organ)
leads to an imbalance between factors that control bone homeostasis
The myeloma cell will cause overproduction of ___-_ (bone resorbing-destruction)
and
growth factor ____ (for bone -forming) is dimished
this results in….
The myeloma cell will cause overproduction of RANK-L (bone resorbing-destruction)
and
growth factor OGP (for bone -forming) is dimished
this results in….
osteoclastogenesis and osteolysis
What is the diagnostic criteria for Multiple Myeloma?
clonal plasma cells >10% on bone marrow biopsy
A monoclonal antibody in either sreum or urine
End organ damage
Current therapies for: non-Hodgkin Lymphoma?
chemotherapy
antibody - Rituxan
radiation - limited
Bone marrow transplant
A treatment: Bortezimib of MM
Inhibits the ___ proteosome (complex that marks proteins for degradation)
plasma cells are _____ secreting factories - handling large quantities of immunoglobulin - so are especially senesitive to this drug
Bortezimib of MM
Inhibits the 26S proteosome (complex that amrks proteins for degradation)
plasma cells are protein secreting factories - handling large quantities of immunoglobulin - so are especially senesitive to this drug
true or False
All B cells express CD20
true
But not plasma cells!
Rituximab is a monoclonal anti-___antibody
Rituximab is a monoclonal anti-CD20 antibody
All mature B cells express CD20 (but not plasma cells - so no good for dealing with Mulitple Myeloma)
The drug ABT-263 blocks the binding site and displaces the apoptosis-inducing __protein
The drug ABT-263 blocks the binding site and displaces the apoptosis-inducing BH3 protein
Monoclonal antibodies represnt a pure population of antibodies with one target specificity make by clonal population of antibody secreting plasma cells
What is the theraputic potential of these?
extrememly well-tolerated
long-lives - half life of several weeks
very specific and selective
THe problem with mAbs rasied in mouse is…
seem as forgein in humans and eventually rejected
short serum half life
because their constant region domains are mouse derived they is a lack of some important effector fnctions in humans
Humanisation of mAbs, to avoid anti-mAb immune reaction in the patient involves…
replacing mouse sequences with human sequnces in vitro
Humanisation II: you can also make mAbs in transgenic mice whose Ig genes have been replaced with ______ Ig genes
Human Ig genes
Humanisation III:
Infect patients memroy B cells with ___
cells become _____
Advantage being its not rejected by patients and captures antibody epcificities that were effective in protecting the donor from past infection
Humanisation III:
Infect patients memroy B cells with EBV
cells become immortal
Advantage being its not rejected by patients and captures antibody epcificities that were effective in protecting the donor from past infection
True or False
Liposome (that can be loaded with drugs/toxins) can be added to mAbs, along with radionucleotides and immunocytokines
true
true or False:
Antibodies can be engineered to have two diferent variable regions (specificities)
I.e one to attach to the tumour cell, one to attract killer cells
True
TNF antibodies work by binding to The ___ _______ and bokcing the _____ - helps to reduce the cascade inflammation
TNF antibodies work by binding to The TNF receptor and blocking the ligand (which is TNF) from working - helps to reduce the cascade inflammation
How does Anti-Vegfa agents (bevacizumab) assist with cancer treatment?
An anti-angiogenensis agent - blocks the formation of new blood vessels so large tuour masses cannot grow at new sites
how do Anti-Her2 agents (trastuzumab) work
Signals through cytoplasmic tyrosine kinase domain when it sees its ligand, neuregulin
used for Her2+breast tumours
Complement mediated lysis can be signalled by ____
antibodies
Nk cells recognise antibodies attached to cancerous cells and bind with FcR
true or False:
IgG mAbs do this best?
true
true or false
rituximab started as a cancer therapy but is now used widely to target autoimmune diseases - including rheumatoid artritis
true
Ipiimumab (anti CtLa4) blocks a ______ receptor on __-cells, promotung acivation efficacy in metastatic meanoma
Ipiimumab (anti CtLa4) blocks a negative receptor on T cells, promotung acivation efficacy in metastatic meanoma
CTLa4 - T cells express it. sees the ligand, and that shuts down the t cells activation
Inhibition of a negative signal
What are some limitations of mAbs?
Unpredictable effects
Cardiotoxicity
infections
acute anaphylaxis
Modifying both the mAbs and the protocols are aimed at minimising these problems
What steps are involved with Anti-CD19 CAR T cell therapy?
) collect white blood cells for T cel acivtion and introdution of CAR gene vector
1) collect white blood cells for T cel acivtion and introdution of CAR gene vector (chimeric receptor)
2) Deplete patients lymphocytes with chemotherapy
3) re-infuse modified patient T cells
CAR:Artificial T cell receptors (also known as chimeric T cell receptors, chimeric immunoreceptors, chimeric antigen receptors (CARs)) are engineered receptors, which graft an arbitrary specificity onto an immune effector cell. Typically, these receptors are used to graft the specificity of a monoclonal antibody onto a T cell; with transfer of their coding sequence facilitated by retroviral vectors.
Il-1beta is a pro-___________ cytokine that drives ___________ and causes systemic signs of inflammation, such as fever,pain and in chronic inflammation - tissue damage
Monoclonal anti-IL1beta acts by _______ ______ and blockade (same as anti-TNF and anti-VEGFA)
Il-1beta is a pro-inflammatory cytokine tha drives inflammation and causes systemic signs of inflammation, such as fever,pain and in chronic inflammation - tissue damage
Monoclonal anti-IL1beta acts by ligant binding and blockade (same as anti-TNF and anti-VEGFA)
