Flashcards in Immunomodulators_New Deck (22):
Define Monoclonal antibodies
Derived from 1 B Cell Fused with Multiple myeloma tumor cell
Cloned B cells grow forever to produce same antibody from original B cell
Procedure for antibody production
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
How are monoclonal antibodies used anti-inflammatory agents?
Monoclonal Abs against mediators of inflammation + receptors/proteins in inflammatory response
Targets of monoclonal antibodies for anti-inflammaotry
CD11a (T cell activation/migration)
alpha-2 integrin (lymphocyte migration)
made entirely from immunized mice
mouse VL and VH domains, but human C domains
only the CDR’s of the V domain are mouse
Disadvantages of mouse monoclonal antibody
1) used only once in patient
2) subsequent uses limited by production of HAMA (human anti-mouse antibody)
Disadvantages of chimeric monoclonal antibody
Can be used more than once
but use limited by production of Human anti-chimeric mab
Why use human mAB
can be used many times in same patient
Define NK cells (large granular lymphocytes)
1) Have receptors for stress markers on growth-dysregulated cells
2) Have Fc receptors for IgG on tumor cells
NK cells bind Fc of IgG on tumor cells
Activates apoptosis of tumor cell
effect of Class I MHC expression levels on susceptibility of target cells to CTL and NK cells
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
Discuss the use of growth factors in bone marrow transplantation
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
What does BiTE stand for?
Bispecific T-cell Engager
How does BiTE work?
2 single-chain engineered antibodies, one against CD19 and one against CD3, bind to T cells in lymphoma and cause tumor cell death
What drug uses BiTE?
What does CAR stand for?
chimeric antigen receptor
How are CARs used to treat CA?
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
LO 7. Discuss the use of modified (drugs, isotopes) monoclonal antibodies in tumor diagnosis or therapy.
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