Immunomodulators_New

Question 1

Define Monoclonal antibodies

Answer 1

Derived from 1 B Cell Fused with Multiple myeloma tumor cell

Cloned B cells grow forever to produce same antibody from original B cell

Question 2

Procedure for antibody production

Answer 2

1) Immunize mouse with antigen you want antibody for
2) Wait for IgG switch in mouse
3) Cut out spleen, distribute 1 cell/well
4) Add myeloma cells and wait for cell fusion
5) Add culture medium with desired antigen and select hybrid based on specificity

Question 3

How are monoclonal antibodies used anti-inflammatory agents?

Answer 3

Monoclonal Abs against mediators of inflammation + receptors/proteins in inflammatory response

Question 4

Targets of monoclonal antibodies for anti-inflammaotry

Answer 4

TNF-a
IL-2 receptor
CD11a (T cell activation/migration)
IgE
anti-CD3
alpha-2 integrin (lymphocyte migration)

Question 5

Murine mAb:

Answer 5

made entirely from immunized mice

Question 6

Chimeric mAb

Answer 6

mouse VL and VH domains, but human C domains

Question 7

Humanized mAb

Answer 7

only the CDR’s of the V domain are mouse

Question 8

Human mAb

Answer 8

fully human

Question 9

Disadvantages of mouse monoclonal antibody

Answer 9

1) used only once in patient

2) subsequent uses limited by production of HAMA (human anti-mouse antibody)

Question 10

Disadvantages of chimeric monoclonal antibody

Answer 10

Can be used more than once

but use limited by production of Human anti-chimeric mab

Question 11

Why use human mAB

Answer 11

can be used many times in same patient

Question 12

Define NK cells (large granular lymphocytes)

Answer 12

1) Have receptors for stress markers on growth-dysregulated cells
2) Have Fc receptors for IgG on tumor cells

Question 13

Define ADCC

Answer 13

NK cells bind Fc of IgG on tumor cells

Activates apoptosis of tumor cell

Question 14

effect of Class I MHC expression levels on susceptibility of target cells to CTL and NK cells

Answer 14

Both NK and CTLs have MHC class 1 receptors

But NK cells inactivated by interaction w/ MHC class 1

Therefore, CTL kill cells with lots of MHC class 1

NK kills tumor cells that downreg MHC class 1

Question 15

Discuss the use of growth factors in bone marrow transplantation

Answer 15

Use G-CSF or GM-CSF to induce proliferation of Hematopoietic stem cells normally at low [ ] in bone marrow

Also use G-CSF/GM-CSF to help transplant patient speed up recovery

Question 16

What does BiTE stand for?

Answer 16

Bispecific T-cell Engager

Question 17

How does BiTE work?

Answer 17

2 single-chain engineered antibodies, one against CD19 and one against CD3, bind to T cells in lymphoma and cause tumor cell death

Question 18

What drug uses BiTE?

Answer 18

blinatumomab (Blincyto)

Question 19

What does CAR stand for?

Answer 19

chimeric antigen receptor

Question 20

How are CARs used to treat CA?

Answer 20

bind them to T cells removed from CA pts using lentiviruses, then replace the cells; this allows transformed CTLs to bind tumor targets with high affinity and specificity w/o MHC restriction

Question 21

LO 7. Discuss the use of modified (drugs, isotopes) monoclonal antibodies in tumor diagnosis or therapy.

Answer 21

Abs to tumor-associated antigens can activate complement or ADCC; ibritumomab tiuxetan can be used to fluorescently ID and then treat tumors; ipilimumab is used to bind to VEGF

Question 22

Name 8 major drugs used in organ transplantation and how they work.

Answer 22

1. azathioprine (decreased DNA synth. and mRNA transc.)
2. mycophenylate mofetil (same as azathioprine, less tox)
3. glucocorticoids (anti-inflamm)
4. cyclosporine A (decrease IL-2 production and lessen stim of T cells)
5. tacrolimus (synergizes with cyclosporine A)
6. sirolimus (rapamycin- binds FKBP-12 to inibit mTOR and T cell activation)
7. anti-thymocyte globulin (ATGAM)
8. mAbs (against CD3 and IL-2)