Blockade of cytotoxic T-lymphocyte antigen-4 as a new therapeutic approach for advanced melanoma

Abstract

Introduction: The incidence of melanoma continues to rise, and prognosis in patients with metastatic melanoma remains poor. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) serves as one of the primary immune check points and downregulates T-cell activation pathways. Enhancing T-cell activation by antibody blockade of CTLA-4 provides a new approach to overcome tumor-induced immune tolerance. Recently, anti-CTLA-4 therapy demonstrated significant clinical benefits in patients with metastatic melanoma, which led to the approval of ipilimumab by the FDA in early 2011.

Areas covered: The fundamental concepts underlying CTLA-4 blockade-potentiated immune activation are presented in this paper, along with the scientific rationale for and the preclinical evidence supporting CTLA-4-targeted cancer immunotherapy. It also provides an update on clinical trials with anti-CTLA-4 inhibitors and discusses the associated autoimmune toxicity.

Expert opinion: Given that overall survival is the only validated end point for anti-CTLA-4 therapy, the clinical implications of the antigen or tumor-specific immunity in patients remain to be clarified. Additional research is necessary to elucidate the prognostic significance of immune-related side effects and significantly optimize the treatment regimens. An improved understanding of the mechanisms of action of CTLA-4 antibodies may also culminate in wide-ranging clinical applications of this new therapy for other tumor types.

Keywords:

• CTL-A blockade
• cytotoxic T-lymphocyte-associated antigen
• overall survival
• T-cell activation
• tumor immunity

Notes

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