B33, antibodies and fusion proteins Flashcards
What are the antibody drug suffixes?
-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
anti-TNF-alpha abs
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
TNF-alpha antibodies
Indications and SEs
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
Anakinra
MoA
Indications
SEs
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
Canakinumab
MoA
Indications
anti IL-1beta antibody
Rx:
Juvenile rheumatoid arthritis
Tocilizumab
MoA
Indications
SEs
Anti-IL-6 ab
Indications:
Moderate to severe RA, as adjunct therapy to the DMARDs.
Natalizumab
Vedolizumab
MoA and indications
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.
Abatacept
MoA
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.
Abatacept
indications and SEs
Abatacept Rx:
- Rheumatoid arthritis
- Juvenile idiopathic arthritis
- Psoriatic arthritis
SEs:
Infections
Drug tolerance from endogenous neutralizing antibodies.
Belatacept
2nd gen costimulator blocker
Also a fusion protein that blocks the CD80/CD86 receptor on APCs
Rx:
for Kidney transplants
Basiliximab
and
Daclizumab
Anti-CD25 antibody. The alpha chain of the IL-2 receptor on activated lymphocytes.
Indicated for transplant immunosuppression, often in conjunction with belatacept.
What mab drug inhibits the CD3 antigen?
Indication?
Muromonab-CD3
Rx:
Kidney transplantation.
SEs:
Cytokine release syndrome - flu like syndrome,
with potential for Distributive Shock.
Omalizumab
target, indications.
Anti-Fc portion of IgE antibodies
Reduces circulating IgE by 90%
Rx:
Severe bronchial asthma
Chronic urticaria
Eculizumab
Anti- C5
Inhibits complement activation
Rx:
Paroxysmal Nocturnal Hemoglobinuria
Atypical hemolytic uremic syndrome
What are the anti B-cell abs
Rituximab and Ocrelizumab, bind the CD-20 antigen.
What are the T-cell inhibiting abs
Abetacept
Basiliximab
Daclizumab
Muromonab-CD3
Alemtuzumab
Anti CD52, found on all lymphocytes, NK cells, and macrophages.
Depletes both B and T cells
Used for Multiple sclerosis,
Severe marrow suppression
What are the ALGs and ATGs?
Anti lymphocyte and anti thymocyte globulins
Polyclonal abs raised in rabbits or horses against human lymphocytes or thymocytes.
ALGs, ATGs indications and SEs
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
What is serum disease
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.
Rituximab
MoA
Indications
SEs
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
Anti-tumor MABs
Bevacizumab
Cetuximab
Rituximab
Trastuzumab
Bevacizumab
Anti-VEGF
Rx:
1) Colon, lung, kidney cancers.
2) Age-related macular degeneration
Cetuximab
anti-EGF receptor
Rx
- RA
- Non-Hodgkin lymphoma
- CLL
Trastuzumab
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
