Cell based therapies II

Question 1

Treg therapeutic use?

Answer 1

Insert them into people w/ inflamatory diseases?

Question 2

Where can Treg cells be isolated from?

Answer 2

Peripheral blood or umbilical cord blood

Question 3

Effect of knocking out IL10 in a mouse model?

Answer 3

Colitis–> inflammation of the colon and GI tract

Question 4

Effect of infusing treg cells into IL10 deficient mice?

Answer 4

Improvement of disease

Question 5

Effect of infusing tregs into Chrons patients?

Answer 5

Safe, better responses w/ a lower number of tregs

Question 6

T1 diabetes?

Answer 6

Activation of cytotoxic t cells against insulin producing pancreatic beta cells

Question 7

Tregs in T1 diabetes patients?

Answer 7

Only expressing low levels of FoxP3

Question 8

Effect of Tregs having low levels of FoxP3?

Answer 8

Not as immunosuppressive as they could be

Question 9

How did the Treg T1 diabetes therapy work?

Answer 9

Take Tregs out of patient, expand them in culture, put them back in

Question 10

Result of treg therapy on T1 diabetics?

Answer 10

Safe, dampened down immune response, reinstate ability of pancreatic beta cells to produce insulin

Question 11

What is SLE?

Answer 11

systemic lupus

Question 12

What is systemic lupus?

Answer 12

Immune complexes/antibodies against common cellular molecules–> DNA, RNA

Question 13

Treg levels in SLE patients?

Answer 13

Lower than in non-SLE

Question 14

Result of infusing Tregs into SLE patients?

Answer 14

Mixed responses
Difference in response came down to purity of treg population–> can vary the amount of foxp3
Treg cells were inactive bc of high IL17, and werent secreting IL2

Question 15

Result of supplementing inactive Treg cells with IL2?

Answer 15

Can re-establish Treg function

Question 16

Effect of Tregs in RA in mouse model?

Answer 16

Decrease in bone destruction and osteoclast activation in mouse models

Question 17

Effect of dampening TNF on Treg cells in humans?

Answer 17

Dampening TNFa promotes Tregs

Question 18

Limitations of Treg therapy?

Answer 18

Sterility, identity, purity, potency
Stability in peripheral blood, how long they secrete cytokines
Preparation and storage

Question 19

What are mesencymal stem cells?

Answer 19

Adult stem cells w/ limited differentiation potential

Question 20

Main role of mesenchymal stem cells?

Answer 20

Tissue repairing

Question 21

Mesenchymal stem cells effects?

Answer 21

Promote M2 macrophage phenotype, promoting Tregs, suppressing effector t cells and b cells and APCs

Question 22

What do mesenchymal stem cells require?

Answer 22

Inflammatory response–> TNFa and IL1 high levels

Question 23

What don’t mesenchymal stem cells stop?

Answer 23

Normal t cell proliferation against pathogens (goo thing–> wont fully knock out immune system)

Question 24

Immunogenicity of mesenchymal stem cells?

Answer 24

Not v high–>low MHC levels

Question 25

Effect of mesenchymal stem cells not being v immunogenic?

Answer 25

Won't cause an immune response if put into foreign tissue

Question 26

What is graft vs host disease (GVHD)?

Answer 26

Effector t cells in a transplanted organ attack the recipient

Question 27

How were mesenchymal stem cells first used?

Answer 27

TO reduce GVHD

Question 28

MSCs in MS?

Answer 28

Not many +ve results

Question 29

Where is the autoantigen in MS?

Answer 29

Myelin sheath--> results in axonal degradation

Question 30

What is chimeric antigen receptor (CAR) t cell therapy?

Answer 30

T cells are removed from the patient, manipulated with viral vectors (carrying receptors that recognize tumor antigens) Genetically engineered to express receptors to tumor antigens

Question 31

What is Tumor infiltrating lymphocyte (TIL) therapy?

Answer 31

T cells harvested from tumors Isolate tumor infiltrating lymphocytes, take them out, duplicate them and put them back in

Question 32

What is TIL therapy approved for?

Answer 32

Melanoma