Lecture 5

Question 1

Lymphoma presents as a

Answer 1

solid tumour of lymphoid cells

Question 2

Hodgkin’s lymphoma: involves the presense of a type of cell called the

Answer 2

Reed-Sternberg cell.

Question 3

Myeloma/multiple myeloma is a

What is it normally preceded by..

Answer 3

cancer of plasma cells

preceeded by an asymptomatic, premalignant stage of clonal plasma cell proliferation (called MGUS)

Question 4

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:

Answer 4

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

Question 5

Myeloma cels bind to ____ cells in the bone marrow

Answer 5

stromal (connective tissue cells of any organ)

leads to an imbalance between factors that control bone homeostasis

Question 6

The myeloma cell will cause overproduction of ___-_ (bone resorbing-destruction)

and

growth factor ____ (for bone -forming) is dimished

this results in….

Answer 6

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

Question 7

What is the diagnostic criteria for Multiple Myeloma?

Answer 7

clonal plasma cells >10% on bone marrow biopsy

A monoclonal antibody in either sreum or urine

End organ damage

Question 8

Current therapies for: non-Hodgkin Lymphoma?

Answer 8

chemotherapy

antibody - Rituxan

radiation - limited

Bone marrow transplant

Question 9

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

Answer 9

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

Question 10

true or False

All B cells express CD20

Answer 10

true

But not plasma cells!

Question 11

Rituximab is a monoclonal anti-___antibody

Answer 11

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)

Question 12

The drug ABT-263 blocks the binding site and displaces the apoptosis-inducing __protein

Answer 12

The drug ABT-263 blocks the binding site and displaces the apoptosis-inducing BH3 protein

Question 13

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?

Answer 13

extrememly well-tolerated

long-lives - half life of several weeks

very specific and selective

Question 14

THe problem with mAbs rasied in mouse is…

Answer 14

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

Question 15

Humanisation of mAbs, to avoid anti-mAb immune reaction in the patient involves…

Answer 15

replacing mouse sequences with human sequnces in vitro

Question 16

Humanisation II: you can also make mAbs in transgenic mice whose Ig genes have been replaced with ______ Ig genes

Answer 16

Human Ig genes

Question 17

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

Answer 17

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

Question 18

True or False

Liposome (that can be loaded with drugs/toxins) can be added to mAbs, along with radionucleotides and immunocytokines

Answer 18

true

Question 19

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

Answer 19

True

Question 20

TNF antibodies work by binding to The ___ _______ and bokcing the _____ - helps to reduce the cascade inflammation

Answer 20

TNF antibodies work by binding to The TNF receptor and blocking the ligand (which is TNF) from working - helps to reduce the cascade inflammation

Question 21

How does Anti-Vegfa agents (bevacizumab) assist with cancer treatment?

Answer 21

An anti-angiogenensis agent - blocks the formation of new blood vessels so large tuour masses cannot grow at new sites

Question 22

how do Anti-Her2 agents (trastuzumab) work

Answer 22

Signals through cytoplasmic tyrosine kinase domain when it sees its ligand, neuregulin

used for Her2+breast tumours

Question 23

Complement mediated lysis can be signalled by ____

Answer 23

antibodies

Question 24

Nk cells recognise antibodies attached to cancerous cells and bind with FcR

true or False:

IgG mAbs do this best?

Answer 24

true

Question 25

true or false

rituximab started as a cancer therapy but is now used widely to target autoimmune diseases - including rheumatoid artritis

Answer 25

true

Question 26

Ipiimumab (anti CtLa4) blocks a ______ receptor on __-cells, promotung acivation efficacy in metastatic meanoma

Answer 26

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

Question 27

What are some limitations of mAbs?

Answer 27

Unpredictable effects

Cardiotoxicity

infections

acute anaphylaxis

Modifying both the mAbs and the protocols are aimed at minimising these problems

Question 28

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

Answer 28

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.

Question 29

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)

Answer 29

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)