B33, antibodies and fusion proteins

Question 1

What are the antibody drug suffixes?

Answer 1

-momab.
totally murine

-iximab.
chimeric, 75% human, 25% murine
human Fc region, murine antigen binding region

-zumab.
Humanized. 95% human, 5% murine

-umab
totally human

Question 2

anti-TNF-alpha abs

Answer 2

Adalimumab - once/half month
Golimumab - once/month
Infliximab - longest lasting, most common. once per 2 months

Certolizumab pegol - Pegylated anti-TNFa fragments.

Etanercept - two TNFalpha receptor regions fused to human Fc regions

Question 3

TNF-alpha antibodies

Indications and SEs

Answer 3

Indications:

• Severe Rheumatoid arthritis
• Juvenile idiopathic arthritis
• Ankylosing spondylitis
• IBD — except for Ethanercept which is contra’d for ibd.

High risk for infections, esp. intracellular bacteria and viruses.
- Tuberculosis and reactivation hepatitis
- Allergic reactions

Question 4

Anakinra

MoA

Indications

SEs

Answer 4

Anakinra - Anti IL-1 receptor antibody.

Rx:
3rd line for Rheumatoid arthritis
Alternative to TNF-alpha blockers, when DMARDs have failed

SEs:

• Neutropenia
• contraindicated for co-admin with TNF-a blocking abs

Question 5

Canakinumab

MoA

Indications

Answer 5

anti IL-1beta antibody

Rx:
Juvenile rheumatoid arthritis

Question 6

Tocilizumab

MoA

Indications

SEs

Answer 6

Anti-IL-6 ab

Indications:
Moderate to severe RA, as adjunct therapy to the DMARDs.

Question 7

Natalizumab
Vedolizumab

MoA and indications

Answer 7

Integrin inhibitors
Prevent leukocyte extravasation

Natalizumab blocks both CNS and GI integrins,
Rx: Multiple sclerosis and Crohns disease
-has a 1:1000 chance of activating JC polyomavirus and causing Progressive Multifocal Leukoencephalopathy

Vedolizumab only blocks GI.
-Crohns disease,
no PML.

Question 8

Abatacept

MoA

Answer 8

A fusion protein of the CTLA-4 protein with ab Fc region.

the CTLF-4 coreceptor fragment binds CD80/CD86 on APCs.
Acts as a dummy receptor preventing the APCs from binding the CD28 receptor on T-cells and activating them.

Question 9

Abatacept

indications and SEs

Answer 9

Abatacept Rx:

• Rheumatoid arthritis
• Juvenile idiopathic arthritis
• Psoriatic arthritis

SEs:
Infections
Drug tolerance from endogenous neutralizing antibodies.

Question 10

Belatacept

Answer 10

2nd gen costimulator blocker
Also a fusion protein that blocks the CD80/CD86 receptor on APCs

Rx:
for Kidney transplants

Question 11

Basiliximab
and
Daclizumab

Answer 11

Anti-CD25 antibody. The alpha chain of the IL-2 receptor on activated lymphocytes.

Indicated for transplant immunosuppression, often in conjunction with belatacept.

Question 12

What mab drug inhibits the CD3 antigen?

Indication?

Answer 12

Muromonab-CD3

Rx:
Kidney transplantation.

SEs:
Cytokine release syndrome - flu like syndrome,
with potential for Distributive Shock.

Question 13

Omalizumab

target, indications.

Answer 13

Anti-Fc portion of IgE antibodies

Reduces circulating IgE by 90%

Rx:
Severe bronchial asthma
Chronic urticaria

Question 14

Eculizumab

Answer 14

Anti- C5
Inhibits complement activation

Rx:
Paroxysmal Nocturnal Hemoglobinuria
Atypical hemolytic uremic syndrome

Question 15

What are the anti B-cell abs

Answer 15

Rituximab and Ocrelizumab, bind the CD-20 antigen.

Question 16

What are the T-cell inhibiting abs

Answer 16

Abetacept
Basiliximab
Daclizumab
Muromonab-CD3

Question 17

Alemtuzumab

Answer 17

Anti CD52, found on all lymphocytes, NK cells, and macrophages.

Depletes both B and T cells

Used for Multiple sclerosis,

Severe marrow suppression

Question 18

What are the ALGs and ATGs?

Answer 18

Anti lymphocyte and anti thymocyte globulins

Polyclonal abs raised in rabbits or horses against human lymphocytes or thymocytes.

Question 19

ALGs, ATGs indications and SEs

Answer 19

Indications:
Are THE most effective agents at preventing acute graft rejection.

Used to pre-treat bone-marrow prior to transplant, to reduce incidence of graft v host disease.

SEs
High rate of side effects, so only used in high likelihood of rejection. 
- Serum disease,
- GI irritation
- Dyspnea

Question 20

What is serum disease

Answer 20

type 3 HSR, self-limiting syndrome caused by immune complex formation against components of the ALG or ATG solution (or any solution administered to patients that is derived from other serum sources, such as IVIG)

  - fever, urticaria and other rashes, joint pain, lymphadenopathy of nodes draining the injection site.

Question 21

Rituximab
MoA
Indications
SEs

Answer 21

Rx: 
•CD20 positive NH-lymphoma
•Chronic Lymphocytic Leukemia
•Adjunct for moderate/severe Rheumatoid arthritis, usually along with MTX
•Vasculatides  
     o	 Wegener’s granulomatosis, 
     o 	Microscopic polyangiitis. 
•Ocrelizumab – for multiple sclerosis

SEs:
1) Predictable, immediate, infusion reaction, occurs just after infusion in >50% of patients on first iv admin of rituximab. Caused by the rituximab induced release of cytokines from the B cells upon binding the receptor. 
o	Fever
o	Headache
o	Pruritic Skin rash
o	Dyspnea
o	Hypotension
o	Steroid, NSAID, acetaminophen, or antihistamine prophylaxis is indicated to prevent too severe infusion reaction. 

2) Serum sickness. A delayed reaction occurring with 7-10 days due to the type 3 HSR of immune complex deposition in tissues throughout the body. Serum sickness reactions occur from patient’s immune system targeting the non-human portions of murine and chimeric antibodies.
o Fever,
o Rash
o Arthralgia
o Proteinuria
o Lymphadenopathy
o Treat with steroid therapy, alleviated in 1-2 days.

3) Multiple rounds of rituximab can cause lowered blood Immunoglobulin levels, immunosuppression, and infection.
• Hepatitis B reactivation
• Progressive multifocal Leukoencephalopathy PML, due to reactivation of the JC Virus due to immunosuppression

Question 22

Anti-tumor MABs

Answer 22

Bevacizumab

Cetuximab

Rituximab

Trastuzumab

Question 23

Bevacizumab

Answer 23

Anti-VEGF

Rx:

1) Colon, lung, kidney cancers.
2) Age-related macular degeneration

Question 24

Cetuximab

Answer 24

anti-EGF receptor

Rx

• RA
• Non-Hodgkin lymphoma
• CLL

Question 25

Trastuzumab

Answer 25

also an anti-EGFR ab
specifically, the Her2/neu, c-erbB2 receptor tyrosine kinase receptor, highly expressed in some breast cancer.

Rx
breast cancer and some gastric cancer
- a usmle one