mAbs
Summary
Monoclonal antibodies (mAbs) are laboratory-engineered antibodies derived from a single clone of B cells, designed to bind a specific antigen with high specificity. They are widely used therapeutically (e.g., in oncology, autoimmune disease, and infectious disease) and diagnostically (e.g., ELISA, flow cytometry). Naming conventions (e.g., -ximab, -zumab, -umab) indicate the degree of humanization.
Detail
Monoclonal antibodies are produced using hybridoma technology (fusion of an antibody-producing B cell with an immortal myeloma cell) or recombinant DNA technology, allowing mass production of antibodies that recognize a single epitope. This contrasts with polyclonal antibodies, which recognize multiple epitopes on an antigen.
Key classifications by structure/origin: - Murine (-omab): fully mouse-derived, highly immunogenic (rarely used now). - Chimeric (-ximab): mouse variable region + human constant region (e.g., rituximab, infliximab). - Humanized (-zumab): mostly human with mouse CDRs grafted in (e.g., bevacizumab, trastuzumab, omalizumab). - Fully human (-umab): entirely human sequence, lowest immunogenicity (e.g., adalimumab, panitumumab).
Mechanisms of action vary by target: - Direct cytotoxicity/blocking growth signals: trastuzumab (anti-HER2), cetuximab/panitumumab (anti-EGFR). - Immune checkpoint inhibition: nivolumab/pembrolizumab (anti-PD-1), ipilimumab (anti-CTLA-4). - Anti-inflammatory/immunosuppressive: infliximab/adalimumab (anti-TNF-alpha), rituximab (anti-CD20, depletes B cells), basiliximab (anti-IL-2 receptor, used in transplant rejection prophylaxis). - Anti-angiogenic: bevacizumab (anti-VEGF). - Anti-IgE: omalizumab (used in allergic asthma). - Coagulation-related: eculizumab (anti-complement C5, used in PNH).
Clinical significance: mAbs form the backbone of targeted therapy in oncology (reducing off-target toxicity compared to chemotherapy), autoimmune disease management (RA, IBD, psoriasis), transplant medicine, and infectious disease (e.g., palivizumab for RSV prophylaxis, monoclonal antibody cocktails for COVID-19).
Adverse effects/considerations: Risk of infusion reactions, immunogenicity (especially with chimeric/murine antibodies leading to human anti-mouse antibody responses), increased infection risk with immunosuppressive mAbs (e.g., reactivation of latent TB with anti-TNF agents, PML risk with natalizumab), and cardiotoxicity with certain agents (e.g., trastuzumab-associated cardiomyopathy).
High-yield boards association: Know the suffix-based naming system and be able to match mAb names to their targets and clinical indications, as well as characteristic side effects (e.g., TB reactivation with infliximab, PML with natalizumab/rituximab).
Sources
- First Aid for the USMLE Step 1
- Katzung's Basic and Clinical Pharmacology
- Kaplan USMLE Step 1 Pharmacology Lecture Notes
- Robbins Basic Pathology
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.