Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU
Monoclonal antibodies are produced by hybridomas. A hybridoma is a product of cell fusion between:
- normal antibody producing B cell (plasma cell)
- myeloma cell
Typically, spleen cells from an immunized mouse are fused with myeloma cells by using polyethylene glycol (PEG) to produce a hybrid cell line called a hybridoma.
Each hybridoma is descended from a single cell and all the antibodies produced by that cell are identical. These antibodies are called monoclonal antibodies (mAbs).
Monoclonal antibodies (mAbs) nomenclature related to sufix
-omab - murine, only of mouse origin. Murine component is 100%
-ximab - chimeric human/mouse. mAb combines murine mAb variable regions with the constant region of human antibody. Murine component is 30%
-zumab - humanized. mAb combines murine mAb variable regions with a portion of a human IgG molecule. Murine component is less than 10%
-umab - "fully" human mAb cloned into a bacteriophage
-cept - fusion of a receptor to the Fc part of human IgG1
Examples of monoclonal antibodies (mAb) in clinical practice
- Rituximab - against CD20. Used in autoimmune diseases, B cell lymphomas
- Anti-CD20 monoclonal antibody ocrelizumab helps patients with relapsing-remitting multiple sclerosis (MS) (Lancet, 2011).
- Omalizumab - againts FcεRI (cε3). Used in asthma
- Adalimumab - against TNF-α. Used in rheumatoid arthritis
- Palivizumab - against RSV. Used to prevent RSV infection in infants with bronchopulmonary dysplasia
- Mepolizumab - against IL-5. Used in hypereosinophilic syndrome and patients with eosinophilic asthma
- Daclizumab - against IL-2 receptor α chain (CD25). Used to prevent renal allograft rejection
- Natalizumab - against α 4 chain of integrin molecule. Used in multiple sclerosis (MS)
- Abciximab - against integrin αIIβ3. Used in acute coronary syndromes (ACS)
- Anti-IL-17 Receptor Antibody Brodalumab Helps Patients with Psoriasis - NEJM, 2012.
- Anti–Interleukin-17 Monoclonal Antibody Ixekizumab Improves Chronic Plaque Psoriasis - NEJM, 2012.
- Natalizumab-Associated Progressive Multifocal Leukoencephalopathy (PML) - NEJM lists the risk factors
- In 2014, FDA Approved New Drug for Crohn Disease and UC: vedolizumab (Entyvio), an injectable monoclonal antibody. Vedolizumab, an integrin receptor antagonist http://buff.ly/1lFuRtv
References
Online Book of Biologic Therapies (monoclonal antibodies, etc.) by the Clinical Immunology Society
Related reading
Allergy to monoclonal antibodies: cutting-edge desensitization methods - Expert Reviews, 2012.
mAb: If it ends in -mumab, it's a fully human protein, -zumab is humanized (10% mouse), -ximab is chimeric (33% mouse). ACP blog, 2012.
Published: 08/12/2008
Updated: 05/25/2012
Showing posts with label Omalizumab. Show all posts
Showing posts with label Omalizumab. Show all posts
Omalizumab can serve as a bridge to immunotherapy in severe asthma
Author: M. Sandhu, M.D.; V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology
A 14-year-old African American male is referred to the allergy clinic with a severe persistent asthma that is poorly controlled on maximum dose inhaled corticosteroids and a long acting beta-agonist. The patient required oral steroids on 4 separate occasions in the past 2 years.
Past medical history (PMH)
Severe persistent asthma, allergic rhinitis.
Medications
Advair 500/50 one inhalation BID, Singulair 10 mg po daily, albuterol prn, Rhinocort daily, loratidine 10 mg po daily.
Physical examination
VSS.
Skin: no rashes, keratosis, excoriations, or lichenifications.
HEENT: pale boggy turbinates (B).
Chest: slightly decreased air entry (B).
CVS: Clear S1S2.
Abdomen: Soft, NT, ND, +BS.
Extremities: no c/c/e.
What diagnostic tests would you suggest?
His FEV1 values ranged widely from as low as 55% to as high as 89% predicted with the higher FEV1 measurements representing recent oral steroid administration. The average FEV1 excluding those values due to oral steroid administration was 68% predicted. The average ACT score was 21.6
What happened?
Our patient was started on omalizumab and his condition stabilized. Allergen immunotherapy was added 5 months later. The patient was initially built up on immunotherapy followed by monthly maintenance doses. The total overlap period of immunotherapy and omalizumab was 19 months.
The average FEV1 during the 19 month overlap phase was 86% predicted and average ACT score was 23.8. During this time the patient had no ER visits, oral steroid doses or adverse reactions to immunotherapy.
What happened next?
Omalizumab was discontinued after 2 years. The patient has been maintained on immunotherapy alone since that time and has maintained this benefit with an average FEV1 of 103%. His average ACT score has been 23.5, with no oral steroid use. Because of overall improvement, his ICS were tapered from high to medium dose. Currently, the patient’s regimen consists of a medium dose inhaled steroid with a long acting beta- agonist, montelukast, and monthly maintenance immunotherapy.
Final diagnosis
Use of Omalizumab as a bridge to immunotherapy in severe asthma.
Summary
Asthma is the most common chronic respiratory disease, affecting up to 10% of adults and 30% of children (JACI, 2011). Allergen immunotherapy was introduced by Leonard Noon 100 years ago and is the only disease-modifying treatment for allergic individuals (Allergy, 2012).
Both allergen immunotherapy (IT) and omalizumab (anti-IgE antibody) are used to treat persistent perennial allergic asthma. Allergen immunotherapy can lead to long lasting improvement with a typical regimen lasting a set time period of 3-5 years. More severe asthmatic patients are at greater risk for serious and potentially life threatening reactions with allergen immunotherapy. Omalizumab treats perennial allergic asthma, acts synergistically with allergen immunotherapy and reduces anaphylactic reactions associated with immunotherapy. Allergic asthma improvements associated with omalizumab are generally present only while on therapy, and thus therapy may continue indefinitely. Our use of omalizumab is as a bridge to immunotherapy making immunotherapy more effective and safer in high risk severe asthmatics.
Severe asthma - differential diagnosis and management (click to enlarge the image).
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology
A 14-year-old African American male is referred to the allergy clinic with a severe persistent asthma that is poorly controlled on maximum dose inhaled corticosteroids and a long acting beta-agonist. The patient required oral steroids on 4 separate occasions in the past 2 years.
Past medical history (PMH)
Severe persistent asthma, allergic rhinitis.
Medications
Advair 500/50 one inhalation BID, Singulair 10 mg po daily, albuterol prn, Rhinocort daily, loratidine 10 mg po daily.
Physical examination
VSS.
Skin: no rashes, keratosis, excoriations, or lichenifications.
HEENT: pale boggy turbinates (B).
Chest: slightly decreased air entry (B).
CVS: Clear S1S2.
Abdomen: Soft, NT, ND, +BS.
Extremities: no c/c/e.
What diagnostic tests would you suggest?
His FEV1 values ranged widely from as low as 55% to as high as 89% predicted with the higher FEV1 measurements representing recent oral steroid administration. The average FEV1 excluding those values due to oral steroid administration was 68% predicted. The average ACT score was 21.6
What happened?
Our patient was started on omalizumab and his condition stabilized. Allergen immunotherapy was added 5 months later. The patient was initially built up on immunotherapy followed by monthly maintenance doses. The total overlap period of immunotherapy and omalizumab was 19 months.
The average FEV1 during the 19 month overlap phase was 86% predicted and average ACT score was 23.8. During this time the patient had no ER visits, oral steroid doses or adverse reactions to immunotherapy.
What happened next?
Omalizumab was discontinued after 2 years. The patient has been maintained on immunotherapy alone since that time and has maintained this benefit with an average FEV1 of 103%. His average ACT score has been 23.5, with no oral steroid use. Because of overall improvement, his ICS were tapered from high to medium dose. Currently, the patient’s regimen consists of a medium dose inhaled steroid with a long acting beta- agonist, montelukast, and monthly maintenance immunotherapy.
Final diagnosis
Use of Omalizumab as a bridge to immunotherapy in severe asthma.
Summary
Asthma is the most common chronic respiratory disease, affecting up to 10% of adults and 30% of children (JACI, 2011). Allergen immunotherapy was introduced by Leonard Noon 100 years ago and is the only disease-modifying treatment for allergic individuals (Allergy, 2012).
Both allergen immunotherapy (IT) and omalizumab (anti-IgE antibody) are used to treat persistent perennial allergic asthma. Allergen immunotherapy can lead to long lasting improvement with a typical regimen lasting a set time period of 3-5 years. More severe asthmatic patients are at greater risk for serious and potentially life threatening reactions with allergen immunotherapy. Omalizumab treats perennial allergic asthma, acts synergistically with allergen immunotherapy and reduces anaphylactic reactions associated with immunotherapy. Allergic asthma improvements associated with omalizumab are generally present only while on therapy, and thus therapy may continue indefinitely. Our use of omalizumab is as a bridge to immunotherapy making immunotherapy more effective and safer in high risk severe asthmatics.
Severe asthma - differential diagnosis and management (click to enlarge the image).
References
Oral corticosteroids were withdrawn in 74% of severe asthma patients treated with omalizumab- Current Medical Research and Opinion, 2010.
Response to omalizumab after 16 weeks is a predictor of continuing persistent response to omalizumab in asthmatics. Allergy 2011.
Immunotherapy can reduce asthma symptoms and it is possibly as effective as inhaled steroids - Cochrane, 2010.
Published: 03/19/2010
Updated: 01/19/2012
Immunotherapy can reduce asthma symptoms and it is possibly as effective as inhaled steroids - Cochrane, 2010.
Published: 03/19/2010
Updated: 01/19/2012
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