title: Nivolumab in combination with ipilimumab for the treatment of melanoma.
abstract: Melanoma patients develop resistance to most therapies, including chemo- and targeted-therapy drugs. Single-agent therapies are ineffective due to the heterogeneous nature of tumors comprising several subpopulations. Treatment of melanoma with immune-based therapies such as anti-cytotoxic T-lymphocyte activation-4 and anti-programmed death-1 antibodies has shown modest but long-lasting responses. Unfortunately, only subsets of melanoma patients respond to antibody-based therapies. Heterogeneity in lymphocyte infiltration and low frequency of anti-melanoma-reactive T-cells in tumor lesions are partly responsible for a lack of response to antibody-based therapies. Both antibodies have same biological function but they bind to different ligands at various phases of T-cell activity. Thus, combination therapy of antibodies has shown superior response rates than single-agent therapy. However, toxicity is a cause of concern in these therapies. Future identification of therapy-response biomarkers, mobilization of tumor-reactive T-cell infiltration using cancer vaccines, or non-specific targeted-therapy drugs will minimize toxicity levels and provide long-term remissions in melanoma patients.
authors.forename: Rajasekharan
authors.initials: R
authors.lastname: Somasundaram
authors.affiliation: a The Wistar Institute, 3601 Spruce St, Philadelphia, PA19104, USA.
authors.forename: Meenhard
authors.initials: M
authors.lastname: Herlyn
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D058990:Molecular Targeted Therapy; D000077594:Nivolumab; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D000074324:Ipilimumab; D000077594:Nivolumab
keywords: Melanoma; anti-CTLA-4; anti-PD-1; antibody therapy; immune-checkpoint inhibitors