The main therapies for cancer include extensive tumor resection, radiation therapy and chemotherapy. However, the elucidation of molecules related to the development, proliferation, survival and immune escape in cancer cells has improved through recent advances in molecular biology and immunology. Based on these findings, a series of cancer immune therapies has been developed and clinical trials have led to the approval of several drugs. In this article, I summarize the immune checkpoint and immune checkpoint inhibitors that have recently been worthy of note.
Malignant melanomas easily metastasize and are often resistant to conventional classical therapies, i.e., surgery, chemotherapy and radiotherapy, in patients with advanced/metastatic malignant melanoma. In recent years, rapid advances have been made in the immunotherapy of malignant melanoma. New medicines, which have been approved by Federal Drug Administration (FDA), have dramatically improved the clinical outcomes for patients with advanced/metastatic melanoma. Nivolumab is an immune checkpoint inhibitor that targets programmed cell death-1 (PD-1) receptors. PD-1 is expressed on many immune cells, including T cells, B cells and natural killer cells. Engagement of PD-1 with its ligands (PD-L1 and PD-L2) induces functional exhaustion of the cytotoxic immune response. Nivolumab inhibits the PD-1 pathway, and thus activates the cytotoxic immune response. Although the immune checkpoint inhibitor tends to take a few months until it exhibits efficacy, once established, the efficacy often lasts for a long time. However, immune checkpoint inhibitors can have many adverse effects, including autoimmune-related inflammation. In particular, relevant severe adverse effects include interstitial pneumonia, colitis, liver dysfunction, thyroid disorders, and infusion reaction. Other affected organs include the skin, eyes, kidneys and nerves. Furthermore, several cases of fulminant type 1 diabetes mellitus have been reported in 2015 and 2016. Because we cannot predict what kinds of adverse effects will occur or when they will occur, we must observe patients carefully in order to detect any adverse events early on, and initiate appropriate treatments. The development of a number of new therapies will provide benefits for patients with malignant melanoma. Dermatologists must use these new drugs appropriately after determining the correct diagnostic information and providing supporting evidence.
Immunotherapeutics for lung cancer include peptide vaccine therapy, immune cell therapy and immune checkpoint inhibitors. The recent development of immune checkpoint inhibitors has been remarkable. Nivolumab, a human IgG4 PD-1 monoclonal antibody immune checkpoint inhibitor, has demonstrated a clinically-meaningful survival benefit compared with the current standard treatment in patients with advanced previously-treated nonsmall cell lung cancer (NSCLC). However, it is necessary to pay attention to immune-mediated adverse events at the time of treatment. It is essential to immediately establish predictive biomarkers for anti-cancer drug selection in NSCLC patients.
Herein, we report an overview of the clinical trial of an immune checkpoint inhibitor for renal cell carcinoma that will be soon approved by health insurance in Japan. We also provide an overview of the probable approval of immune checkpoint inhibitors for genitourinary tract cancers.
In recent years, advances in cancer immunology research have led to the development of immune checkpoint inhibitors for anticancer treatments against many types of malignant neoplasms. However, immunological approaches have already achieved great success in the treatment of hematological malignancies, due to their specificity. In this review article, we discuss hematological malignancies from the perspective of cancer immunology, along with the advancement of monoclonal antibodies since the advent of rituximab, and the development of immune checkpoint inhibitors.