Monoclonal Antibodies Approved for Cancer Therapy
| Autor: | Baldo, Brian A. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Blinatumomab
Monoclonal antibody adverse events Cetuximab Cancer immunotherapy Anti-CTLA-4 Article Monoclonal antibody targets Ramucirumab Siltuximab Anti-CD20 Daratumumab Obinutuzumab Alemtuzumab Trastuzumab emtansine Necitumumab Antitumor agents Pertuzumab Elotuzumab Panitumumab Ofatumumab Trastuzumab Dinutuximab Ipilimumab Anti-PD-1 Disialoganglioside (GD2) Bevacizumab Nivolumab Monoclonal antibody cancer therapy Catumaxomab Immune checkpoints Brentuximab vedotin Monoclonal antibodies Ibritumomab tiuxetan Denosumab Infusion reactions Rituximab Pembrolizumab Checkpoint inhibitors Anti-IL-6 |
| Zdroj: | Safety of Biologics Therapy |
| Popis: | Twenty-four monoclonal antibodies (mAbs) targeted to a total of 16 different antigens are currently approved for the treatment of an increasing number of cancers. Six are directed against antigens expressed on B lymphocytes (ibritumomab tiuxetan, obinutuzumab, ofatumumab, and rituximab to CD20, brentuximab vedotin to CD30, and alemtuzumab to CD52); cetuximab, panitumumab, and necitumumab target EGFR; bevacizumab and ramucirumab are specific for VEGF and VEGFR2, respectively; pertuzumab, trastuzumab, and ado-trastuzumab target HER2; nivolumab and pembrolizumab are directed to the programmed cell death protein 1 (PD-1); and denosumab, ipilimumab, siltuximab, and dinutuximab recognize RANKL, CTLA-4, IL-6, and the disialoganglioside (GD2), respectively. In November 2015, the FDA approved daratumumab, the first anti-CD38 mAb and the first mAb to be approved for the treatment of multiple myeloma. Elotuzumab, targeted to the receptor SLAMF7, was also given approval for multiple myeloma soon after. Two antibodies are bispecific: the rat-mouse chimera, catumaxomab, recognizes both EpCAM and CD3, while blinatumomab, a bispecific T-cell-engaging (BiTE) fusion protein, targets both CD19 and CD3. Although mAbs used for cancer immunotherapy are generally better tolerated than small molecule chemotherapeutic drugs, their range of adverse effects is still wide and varied from mild gastrointestinal symptoms and transient rashes to severe cytopenias; anaphylaxis; autoimmunity; pulmonary, cardiac, hepatic, kidney, neurological, and embryofetal toxicities; and rare life-threatening toxidermias. Because of their immunogenic potential, mAbs generally carry warnings of immune reactions, especially anaphylaxis, but the observed incidences of such reactions are actually quite small. Cytopenias occur in some patients treated with mAbs during anticancer immunotherapy, but the underlying mechanisms frequently remain unexplored. Type II and III hypersensitivities induced by mAbs may be underdiagnosed. Severe infusion reactions have been reported for all the mAbs although some show a much higher incidence with the chimeric rituximab and humanized trastuzumab antibodies being the leading offenders. Distinguishing features in the literature between cytokine release syndrome and severe infusion reactions are often not clear. At least ten of the currently approved mAbs for cancer therapy show some pulmonary toxicity. These pulmonary adverse events can be grouped into four categories: interstitial pneumonitis and fibrosis, acute respiratory distress syndrome (ARDS), bronchiolitis obliterans organizing pneumonia (BOOP), and hypersensitivity pneumonitis. Cardiac adverse events, including congestive heart failure, decreased LVEF, myocardial infarction, cardiac arrest, and arrhythmias, have occurred with at least 11 of the mAbs. Papulopustular eruptions, cutaneous reactions that are not immune-mediated, as well as a range of other adverse mucocutaneous effects, are elicited in a large proportion of patients by mAbs targeted to EGFR. Other rare but mAb-induced serious adverse events are tumor lysis syndrome and progressive multifocal leukoencephalopathy. |
| Databáze: | OpenAIRE |
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