Immunotherapy Agents

Question 1

Cyclosporine

Answer 1

Calcineurin inhibitor
Mx: binds cyclophilin A, complex inhibits calcineurin, decreased IL2, IL2R, c-myc, h-ras, and may increase TGF-B
Selective for T lymphocytes
Use: prevention/treatment organ rejection, treat autoimmune disorders
Adverse: Nephrotoxicity, hypertension, hepatotoxicity

Question 2

Tacrolimus

Answer 2

Calcineurin inhibitor
Mx: bind FKBP, complex inhibits calcineurin
Use: similar to cyclosporine
Adverse: Nephrotoxicity, neurotoxicity, hypertension, diabetes

Question 3

Sirolimus and Everolimus

Answer 3

Mx: binds FKBP, but inhibits mTOR which is important for T cell proliferation
Use: similar to cyclosporine
Adverse: increase in serum cholesterol and triglycerides, delayed graph function and wound healing, anemia, leukopenia, thrombocytopenia

Question 4

Glucocorticoids - Prednisone & Prednisolone

Answer 4

Mx: Inhibit T cell prolieration & immunity, inhibits expression of cytokine genes, T cells > B cells
Use: prevent organ rejection, treat autoimmune disease, anti-inflammatory action important

Question 5

Azathioprine

Answer 5

Mx: Converted to 6-mecaptopurine, inhibits purine synthesis inhibiting T cell proliferation
Use: adjunct to prevent transplant rejection
Drug interax: Allopurinol decreases clearance so reduce Azathioprine dose
Advese: Bone marrow suppression

Question 6

Mycophenolate Mofetil

Answer 6

Mx: Converted to mycophenolic acid, competitive inhibitor of inosine monophosphate dehydrogenase, inhibit de novo synthesis of guanosine, T & B lymphocytes require this pathway and are selectively sensitive
Use: prophylaxis of transplant rejection,
Adverse: GI, leukopenia
Drug interax.: antacids decrease absorption

Question 7

Antithymocyte Globulin

Answer 7

polyclonal antibody from horses or rabbits immunized with human thymocytes
Mx: Induces T cell lymphopenia and decreases T cell function
Use: prevent acute allograft rejection
Adverse: serum sickness, nephritis, chills, fever, rash

Question 8

Muromonab-CD3

Answer 8

Mouse Monoclonal antibody against CD3
Mx: induces internalization of T cell receptor, decrease circulating T cells
Use: reverse transplant rejection
Adverse: cytokine release syndrome, CNS toxicity, anaphylaxis

Question 9

Daclizumab & Basiliximab

Answer 9

Humanized monoclonal antibodies against IL2R
Mx: bind IL2R and inhibit T cell activation
Use: prophylaxis transplant rejection

Question 10

Alemtuzumab

Answer 10

Humanized monoclonal antibodies against CD52
Mx: binds CD52 on B cells, T cells, monocytes, macrophages, NK cells and induces apoptosis
Use: Chronic lymphocytic leukemia

Question 11

Efalizumab

Answer 11

Humanized monoclonal antibody against LFA-1
Mx: binds CDIIa subunit of LFA-1 blocking T cell adhesion and activation
Use: Prevent transplant rejection, treat psoriasis

Question 12

Tocilizumab

Answer 12

Humanized monoclonal antibody against IL6R
Mx: Inhibits IL6 actions
Use: juvenile rheumatoid arthritis

Question 13

Rituximab

Answer 13

Humanized monoclonal antibody against CD20
Mx: Binds to CD20 on B cells, induces lysis
Use: treat chronic lymphoid leukemia, non Hodgkin’s lymphoma, rheumatoid arthritis

Question 14

Infliximab

Answer 14

mouse-human chimeric monoclonal antibody
Mx: binds and neutralizes TNF
Use: rheumatoid arthritis, psoriasis, Crohn’s disease

Question 15

Adalimumab

Answer 15

Hmanized monoclonal antibody
Mx: binds and neutralizes TNF
Use: rheumatoid arthritis, psoriasis, Crohn’s disease

Question 16

Entenercept

Answer 16

Fusion protein of ligand binding domain of TNF and IgG fragment
Mx: binds and neutralizes TNF
Use: Rheumatoid arthritis, psoriasis, Crohn’s disease

Question 17

Alefacept

Answer 17

LFA-3/IgG fusion protein
Mx: binds CD2 on T cells and prevents adhesion and activation of T cells
Use: psoriasis

Question 18

Abatacept/Belatacept

Answer 18

CTLA-4/IgG fusion protein
Mx: Binds CD80 and CD86 inhibiting costimulation and activation of T cells
Use: Abatacept - juvenile idiopathic/rheumatoid arthritis
Belatacept - prevent organ transplant rejection

Question 19

Immunoglobulin

Answer 19

Contains all subclasses (IgG > IgM)

Question 20

Bacillus Calmette-Guerin Vaccine

Answer 20

Live attenuated strain of Mycobacterium bovis
Mx: stimulates NK cells and T cells
Use: bladder cancer
Adverse: severe hypersensitivity reactions and shock

Question 21

Levamisole

Answer 21

Normally anthelminic drug
Mx: Inhibit T reg cells
Use: immunostimulant in colon cancer

Question 22

Isoprinosine

Answer 22

Mx: Increase NK cell cytotoxicity and activity of T cells and monocytes
Rarely used!

Question 23

Thalidomide

Answer 23

Mx: decreases circulating TNF-a
Use: severe refractory arthritis, erythema nodosum leprosum
Contraindicated in pregnancy - teratogenic (birth defects)

Question 24

Interferon a

Answer 24

Mx: activates macrophages, NK cells, and T cells
Use: cancers, Hepatitis B & C
Adverse: Flu-like symptoms, Pulmonary Hypertension

Question 25

Interleukin 2

Answer 25

Mx: activates cellular immunity
Use: metastatic melanoma, renal cell carcinoma, and AIDS
Adverse: Severe hypotension and life threatening cardiotoxicity, Pulmonary edema is dose limiting!

Question 26

Granulocyte Colony Stimulating Factor

Answer 26

Mx: Stimulate production of granulocytes and monocytes
Use: reduce neutropenia