Table 2.

Clinically used antibody-based triggering immunomodulatory biologics

Biologic	Type	Mechanism of action	Indications	Immune-related safety warnings
Alemtuzumab	Humanized mAb	Binds to CD52 on leukocytes and initiates antibody-dependent cell-mediated lysis	B cell chronic lymphocytic leukaemia	• Boxed warnings for cytopaenias, infusion reactions and infections • Autoimmunity171 and immunogenicity157 reported
Brentuximab vedotin	Chimeric mouse–human mAb	Antibody–drug conjugate (CD30-specific mAb conjugated to MMAE) that induces cell cycle arrest and apoptosis	Hodgkin's lymphoma, systemic anaplastic large cell lymphoma	• Boxed warning for PML • Warning for neutropaenia and infection172 on product label
Catumaxomab	Rat–mouse hybrid mAb	Bispecific antibody; binds to CD3–EpCAM and forms a bridge between cancer cells and T cells	Cancer, malignant ascites	• Boxed warnings for CRS and/or SIRS • Immunogenicity reported173 • Additional monitoring required by the MHRA
Denileukin diftitox	Fusion protein (IL-2 and Diphtheria toxin)	Binds to CD25 of IL-2R and triggers toxin-induced cell death	T cell lymphoma	• Boxed warnings for severe infusion reactions and capillary leak syndrome
Ibritumomab tiuxetan	Mouse mAb	Fab segment of the antibody targets CD20 on B cells, allowing covalently linked radioactive yttrium, which emits a β particle, to destroy the cell	Follicular non-Hodgkin's lymphoma	• Boxed warnings for acute infusion reactions, severe cutaneous and mucocutaneous reactions, and prolonged and severe cytopaenia • Anaphylaxis and immunogenicity reported174
Muromonab-CD3	Mouse mAb	Kills CD3-positive cells by inducing antibody-dependent cell-mediated toxicity and complement-dependent cytotoxicity	Organ transplant rejection	• Boxed warnings for CRS and anaphylactic reactions • Warnings for infections and malignancy on product label • Immunogenicity reported19,175
Ofatumumab	Human mAb	Targets CD20 and facilitates cell lysis due to complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity of B cells	Chronic lymphocytic leukaemia	• No boxed or product label warnings issued • Infections reported176 • Additional monitoring required by the MHRA
Rituximab	Chimeric mouse–human mAb	Binds to CD20 on B cells and triggers B cell lysis by complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity	Non-Hodgkin's lymphoma, chronic lymphocytic leukaemia, rheumatoid arthritis, Wegener's granulomatosis and microscopic polyangitis	• Boxed warnings for acute infusion reactions and/or CRS, tumour lysis syndrome, severe mucocutaneous reactions and PML
Tositumomab	Mouse mAb	Binds to CD20-positive cells and causes cell death through ionizing radiation when it is radiolabelled (131I); also induces complement-dependent and antibody-dependent cell-mediated cytotoxicity	Non-Hodgkin's lymphoma (CD20-positive, follicular)	• Boxed warnings for severe allergic reactions and/or anaphylaxis, and prolonged and severe cytopaenia • Malignancy warning on product label • Immunogenicity reported177
CRS, cytokine release syndrome; EpCAM, epithelial cell adhesion molecule; IL-2R, interleukin-2 receptor; mAb, monoclonal antibody; MHRA, Medicines and Healthcare products Regulatory Agency (UK); MMAE, monomethyl auristatin E; PML, progressive multifocal leukoencephalopathy; SIRS, systemic inflammatory response syndrome.