Biologics - To Treat Chronic Inflammatory Conditions

Vocabulary flashcards covering biologic therapies, their mechanisms of action, and specific antibody targets for chronic inflammatory conditions.

Abatacept

A fusion protein (immunoadhesin) linking the extracellular domain of CTLA-4 to the Fc region of IgG1. It binds to CD80/86 on the APC, preventing the co-stimulatory signal ($CD28-CD80/86$) and full activation of T cells.

Rituximab

A chimeric monoclonal antibody against the CD20 surface protein on mature B cells. It inhibits B-cell proliferation and differentiation, reduces CD40 and CD80 expression, and inhibits TNF-\text{̑} release from macrophages while increasing IL-10.

Vedolizumab

A humanised IgG1 monoclonal antibody that targets the \text{̑}4\text{̀}7 cell adhesion molecule (integrin). It prevents the activation, adhesion, and migration of immune cells to sites of inflammation.

Omalizumab

A humanised IgG1 monoclonal antibody targeting the constant region of circulating IgE. It prevents IgE from binding to the Fc\text{̄}R1 on mast cells and basophils and reduces Fc\text{̄}R1 expression on effector cells.

TNF-\text{̑} (Tumor Necrosis Factor alpha)

A central pro-inflammatory cytokine synthesized by macrophages, lymphocytes, and other tissues. Activation of its receptor leads to NF\text{̀}B activation, production of IL-1 and IL-6, and expression of adhesion molecules like ICAM-1.

Etanercept

A fusion protein (immunoadhesin) consisting of two extracellular domains of the TNF-\text{̑} receptor fused to IgG1. It acts as a soluble receptor decoy that neutralizes TNF-\text{̑} to reduce joint destruction in RA.

Certolizumab Pegol

A PEGylated Fab fragment of a humanised IgG1 antibody against TNF-\text{̑}. It lacks an Fc region to better penetrate tissue, using polyethylene glycol (PEG) to resolve the resulting shorter half-life.

Infliximab

A chimeric IgG1 monoclonal antibody (mAb) directed against TNF-\text{̑}.

Adalimumab and Golimumab

Human IgG1 monoclonal antibodies that bind to TNF-\text{̑}, preventing it from binding to its receptors.

Mepolizumab

A human IgG1 monoclonal antibody against cytokine IL-5. It prevents IL-5 from binding to receptors abundant on eosinophils, thereby reducing their proliferation, maturation, and activation.

Tocilizumab

A humanised IgG1 mAb against the IL-6 receptor ($IL-6R$). It acts as a receptor antagonist for both soluble and transmembrane forms, blocking activation and signaling via the JAK-STAT pathway.

Secukinumab

A human IgG1 monoclonal antibody against $IL-17A$. It prevents $IL-17A$ containing homodimers or heterodimers from binding to the $IL-17RA$ and $IL-17RC$ receptor complex.

Ustekinumab

A fully human IgG1 monoclonal antibody against the $p40$ subunit shared by IL-12 and IL-23. It blocks TH1 differentiation (via IL-12) and TH17 proliferation and activation (via IL-23).

Strategy 1 of Biologics

Preventing cell-to-cell interactions required for the recruitment and activation of immune cells at the site of response.

Strategy 2 of Biologics

Blocking cytokine/receptor association to prevent the initiation and maintenance of the inflammatory immune response.