An innovative breakthrough in cancer immunotherapy: potential of pembrolizumab
- Institute of Experimental and Clinical Medicine of the National Medical University named after Bogomolets A.A., Kyiv
Summary. Immunomodulatory drugs of monoclonal antibodies are innovative immunotherapeutic agents in oncology with fundamentally new mechanism of action. Innovation of the approach is exactly in philosophy of the tumor immunotherapy, which includes not a direct destruction of tumor cells under the influence of the drug, which inevitably accompanied with a number of severe side effects, but an elimination of the key mechanism of tumor induced immunosuppression, with the help of which neoplasia back out of immune surveillance. Pembrolizumab, humanized monoclonal antibody IgG4 to PD-1 molecule, is the most perfect representative of this group of immunobiological antitumor agents. Through blocking of the co-inhibitory receptor PD-1 on the surface of the specific cytotoxic CD8+ T-lymphocytes, which infiltrating a tumor, it provides a resistance of the effector immunocompetent cells to the immunosuppressive effects of the malignant cells, which implemented through the PD-1:PD-L1 и PD-1:PD-L2 axis. The drug cancels tumor-induced selective cell immunodeficiency, providing to the immune system a possibility to realize an effective cytotoxic response against neoplasia. The results of clinical trials allow to recommend pembrolizumab in patients with inoperable or unresponsive to ipilimumab and BRAF inhibitor metastatic melanoma. There are encouragingly preliminary results of trials of pembrolizumab in small cell lung cancer. The success of innovative immunotherapy in oncology open up promising prospects of the effective, safe and, most importantly, physiologically based treatment of the malignant human neoplasms.