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.

Keywords: Melanoma; anti-CTLA-4; anti-PD-1; antibody therapy; immune-checkpoint inhibitors.