[Recent Development of Therapies for Melanoma Using Immune Checkpoint Blockades].
Melanoma is a highly immune tumor, and tumor-specific T lymphocytes are occasionally induced. Recent progress in tumor immunology has made it possible to clinically develop new medicines targeting immune checkpoint molecules, such as cytotoxic T lymphocyte antigen 4(CTLA-4), programmed cell death 1(PD-1), and programmed cell death 1 ligand 1(PD-L1). CTLA-4 is expressed on naïve T cells and regulatory T cells. Ipilimumab, an anti-CTLA-4 antibody, shows a distinct durable clinical benefit by inhibiting the immunosuppressive function of CTLA-4. PD-1, which is expressed on activated T cells, inhibits T cell responses against tumor cells. The antibodies against PD-1, nivolumab and pembrolizumab, produce anti-tumor responses in melanoma and other cancers due to T cell reactivation. Furthermore, clinical trials of combination therapies using immune checkpoint blockades with molecularly targeted therapies and other chemotherapeutic agents are being conducted. However, immune checkpoint blockades frequently cause immune-related adverse events. Targeted therapies to immune checkpoint molecules are expected to be promising strategies for treatment of melanoma and other cancers.
Dept. of Dermatology, Shinshu University School of Medicine.
Ryuhei
R
Okuyama
D000906:Antibodies / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D058990:Molecular Targeted Therapy; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology
D000906:Antibodies; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D060908:CTLA-4 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor