What does monoclonal mean in medicine?

What is Monoclonal in Medicine?

Monoclonal refers to antibodies or proteins derived from a single clone of cells that are identical and target a specific antigen with high specificity. 1, 2

Definition and Characteristics

• Monoclonal antibodies (mAbs) are recombinant proteins produced by a single clone of cells, engineered to recognize and bind to a single specific antigen 2
• They are homogeneous molecules with identical structure and binding properties, unlike polyclonal antibodies which come from multiple cell lineages 3
• The term "mono" refers to single and "clonal" refers to the cell lineage origin, indicating all antibodies are identical copies from the same parent cell 3

Production Methods

• Monoclonal antibodies are typically produced using hybridoma technology, first developed by Köhler and Milstein in 1975 3
• The process involves:
  • Immunization of an organism with a specific antigen 3
  • Isolation of antibody-producing B cells from the spleen 3
  • Fusion of these B cells with immortal myeloma cells to create hybridomas 3
  • Selection and cloning of hybridoma cells that produce the desired antibody 3
• Modern techniques include phage display technology and single B cell technologies for more efficient monoclonal antibody discovery 4, 5

Medical Applications

• Therapeutic applications: Monoclonal antibodies are used to treat various diseases including cancer, autoimmune disorders, and infectious diseases 2
• Diagnostic applications: They serve as highly specific tools in laboratory tests and imaging 6
• Site-specific drug delivery: Monoclonal antibodies can be used to deliver drugs directly to target cells or tissues 6
• Research tools: They help in identifying specific proteins, cells, or tissues with high precision 6

Types of Monoclonal Antibodies

• Murine (mouse-derived) - first generation, highly immunogenic in humans 5
• Chimeric (part mouse, part human) - reduced immunogenicity 5
• Humanized (mostly human with some mouse components) - further reduced immunogenicity 5
• Fully human - least immunogenic, developed using newer technologies 5
• Antibody-drug conjugates - monoclonal antibodies linked to cytotoxic drugs 5
• Bispecific antibodies - engineered to recognize two different antigens simultaneously 5

Clinical Example: Monoclonal Gammopathy

• Monoclonal gammopathy refers to conditions where a single clone of plasma cells produces an excess of a specific immunoglobulin 7
• In Monoclonal Gammopathy of Renal Significance (MGRS), B cell or plasma cell clones produce nephrotoxic monoclonal immunoglobulins that can damage the kidneys 7
• MGRS is defined as any B cell or plasma cell clonal lymphoproliferation that produces kidney lesions related to monoclonal immunoglobulin, without meeting criteria for specific hematological therapy 7

Advantages of Monoclonal Antibodies

• High specificity for their target antigens 2
• Fewer off-target adverse effects compared to many small molecule drugs 2
• Fewer drug-drug interactions 2
• Potential for increased efficacy through targeted therapy 2
• Can be produced in virtually unlimited supply once the hybridoma is established 6

Important Considerations

• Monoclonal antibodies can have significant clinical impact even when produced by small B cell clones 7
• The term "monoclonal" is often used in contrast to "polyclonal," which refers to antibodies derived from different cell lineages 3
• Modifications to monoclonal antibodies can decrease immunogenicity and increase efficacy 2
• Monoclonal antibodies are typically administered parenterally due to their large molecular size, though research continues on improving oral bioavailability 2