Immunosuppressive Antibodies, Monoclonal Antibodies and Immunostimulants

Question 1

Moving on to the immunosuppressive antibodies. First up are the polyclonal antibodies. They are antilymphocyte and antithymocyte antibodies. What is their MOA?

Answer 1

Antilymphocyte globulin (ALG)
Antithymocyte globulin (ATG)
--produced in horses and sheep by immunization against human thymus cells. Antibodies in these preparations bind to T cells involved in antigen recognition and initiate their destruction by serum complement 
Used to prevent graft vs host reaction

Question 2

The other polyclonal antibodies used are Rho Immune Globulin. What is the MOA?

Answer 2

Preparation of human IgG containing antibodies against the Rho antigen of the red cell

Question 3

Explain hemolytic disease of the newborn in relation to Rho antigen -antibody

Answer 3

Rh negative women will be sensitized to the RH antigen at the time of birth of a Rho positive infant

• -when fetal RBCs leak into the mother’s bloodstream, the immune response will make antibodies to the Rh antigen
• -when mother gets pregnant again, maternal antibody against Rh positive cells is transferred to the fetus during the 3rd trimester and this is life threatening

Question 4

What are uses of Rho immune globulin?

Answer 4

Prevention of Rh hemolytic disease of the newborn

–given to Rh negative mothers, the immune response will be blocked to foreign cells

Question 5

The next immunosuppressive antibodies are monoclonal antibodies. First up is TNF-alpha inhibitors, what are some features?

Answer 5

TNF alpha effects are mediated by TNF receptors (TNF1 and TNF2)
–blocking the binding to receptors on inflammatory cells results in suppression of downstream cytokines and adhesion molecules involved in leukocyte activation

Question 6

An increased risk of what is associated with TNF alpha inhibitors?

Answer 6

Infection or Reactivation of M tuberculosis, hep B virus and invasive systemic fungi

Question 7

Next monoclonal antibody is Infliximab, what are some features?

Answer 7

Binds with high affinity and specificity to human TNF-alpha
–decreases formation of interleukins and adhesion molecules involved in leukocyte activation
Tx:
–RA, psoriatic arthritis, UC and Crohns

Question 8

Third monoclonal antibody is Adalimumab, what are some features?

Answer 8

Human IgG1 anti-TNF monoclonal antibody
–complexes with TNF-alpha and prevents interaction with its receptors
Tx:
RA, Psoriatic arthritis, UC and Crohns

Question 9

Fourth monoclonal antibody is Etanercept, what are some features?

Answer 9

Contains the ligand binding portion of a human TNF-alpha receptor fused to the Fc portion of human IgG1
–Etanercept bind to TNF-alpha and prevents it from interacting with its receptors
Tx:
RA, Plaque Psoriasis and Psoriatic Arthritis

Question 10

What are some effects of the Anti-TNF alpha drugs.

Answer 10

1. Cytopenias
2. Bacterial sepsis and TB (reactivation)
3. Do not give in patients with active infection
4. Screening for latent TB needs to be done
5. Increase the risk for invasion and disseminated infections caused by viral and fungal pathogens
6. Increased risk for malignancies including lymphomas.

Question 11

There are three other monoclonal antibodies. The first is Omalizumab, what are some features?

Answer 11

Anti-IgE recombinant Humanized Monoclonal Antibody
–binds to IgE and prevents IgE from binding to mast cells and basophils, so prevents the release of inflammatory mediators after allergen exposure
Use:
kids over 12 with asthma refractory to inhaled corticoids

Question 12

The second other monoclonal antibody is Basiliximab, what are some features?

Answer 12

Human-mouse IgG that binds to IL-2 receptor on activated lymphocytes
Tx:
prevent renal transplant rejection

Question 13

The third monoclonal antibody is Rituximab, what are some features?

Answer 13

Murine-human monoclonal antibody that binds to the CD20 molecule on B lymphocytes and depletes circulating B cells
Tx:
non-hodgkins lymphoma and CLL

Question 14

Finally there are two other biological immunosuppressive agents, the first is Anakinra. What are some features?

Answer 14

IL-1 receptor antagonist
–recombinant version of the naturally occurring human IL-1RA that prevents IL-1 from binding to its receptor
Tx:
Moderate to severe R arthritis

Question 15

The last immunosuppressive agent is Abatacept, what are some features?

Answer 15

Fusion protein that interferes with T cell activation
Tx:
moderate to severe RA
moderate to severe polyarticular juvenile idiopathic arthritis

Question 16

There is a chart of immunosuppressive agents

Answer 16

:)

Question 17

The last set of drugs are the immunostimulants, what are these agents?

Answer 17

Used for tx of immune deficiency diseases and chronic infectious diseases and cancer

Question 18

The first immunostimulant drug is Aldesleukin, what are some features?

Answer 18

Recombinant Interleukin-2
–endogenous lymphokine that promotes the production of cytotoxic T lymphocytes and activates NK cells
Tx:
–adjunctive treatment of renal cell carcinoma and malignant melanoma

Question 19

The second immunostimulant drug is Interferons, what are some features?

Answer 19

Used in hairy cell leukemia, CLL, malignant melanoma, Kaposi’s Sarcoma, Hep B and C infection
Also for relapsing MS
Tx of Chronic Granulomatous disease