Cetuximab is a human-mouse chimeric monoclonal antibody that targets epidermal growth factor receptor (EGFR). Binding of cetuximab to EGFR inhibits tumor cell growth by a variety of mechanisms, including decreases in kinase activity, matrix metalloproteinase activity, and growth factor production, as well as increased apoptosis. It is approved for use in patients with EGFR-positive head and neck squamous cell carcinoma in combination with radiotherapy or appropriate chemotherapy. It is also approved for treatment of KRAS-negative, EGFR-positive metastatic colorectal cancer in combination with radiotherapy or appropriate chemotherapy, or as a single agent in patients who cannot tolerate certain chemotherapies. Cetuximab may be administered in combination with irinotecan or alone in patients who cannot tolerate irinotecan. HAMAs are generated by about 4% of patients being treated with cetuximab.
Daratumumab binds to CD38, which is over-expressed on myeloma cells. Binding of daratumumab to CD38 on myeloma cells likely induces cell death by apoptosis, complement-dependent cytotoxicity, or antibody-dependent cytotoxicity. It is approved by the FDA for use in multiple myeloma patients who are refractory to standard treatments, although phase III trials are ongoing regarding its use as a frontline therapy. Elotuzumab is FDA approved for the treatment of relapsed multiple myeloma. This Mab binds signaling lymphocytic activation molecule F7 (SLAMF7) on myeloma cells. It enables killing of multiple myeloma tumor cells by antibody-dependent cell-mediated cytotoxicity (ADCC).
Dinutuximab is a ganglioside D2 (GD2)-binding Mab approved for pediatric patients with high-risk neuroblastoma in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA) who achieve at least a partial response to prior first-line multiagent, multimodality therapy. It has a black box warning for serious infusion reactions and neurotoxicity in the majority of patients.
Necitumumab is a Mab directed against epidermal growth factor receptor (EGFR) and approved for use in patients with squamous non-small cell lung cancer in combination with gemcitabine and cisplatin. There is a black box warning for cardiopulmonary arrest and hypomagnesemia.
Ipilimumab (Yervoy) binds to CTLA-4 on T cells, preventing CD80/86 from delivering a suppressive signal to T cells. This has the effect of maintaining T-cell activation. It is approved for the treatment of unresectable or metastatic melanoma and treatment of cutaneous melanoma with regional nodes in the adjuvant surgical setting.
Nivolumab, Pembrolizumab, and Atezolizumab allow potential anti-tumor T cells to remain activated. By binding to the PD-1 marker on T cells, nivolumab and pembrolizumab block the binding of PD ligand-1 (PD-L1) on tumor cells, which suppresses T cell activity. Atezolizumab and avelumab bind to PD-L1 on tumor cells, also interfering with PD-1 signaling in T cells.
Nivolumab is approved for Hodgkin’s lymphoma, renal cell carcinoma, non-small cell lung cancer, and melanoma. Pembrolizumab is approved for the treatment of head and neck cancer, melanoma (and ipilimumab-resistant melanoma), Merkel cell carcinoma, non-small cell lung cancer, and cancers in HIV-positive patients. Atezolizumab is approved for bladder cancer and is in late-stage clinical trials for several other cancer types.