[Immunotherapy of cancer with checkpoint inhibitors : Not only in malignant melanoma]

The newest weapon in cancer therapy is checkpoint inhibition, which is the result of basic immunology research. The success of this therapy is based on the fact that upon light microscopy, many solid tumors harbor lymphocytic cells infiltrating the tumor (TILs), and in many solid tumors, the presence of these TILs are prognostic. Ipilimumab was the first monoclonal antibody developed against a target present on T cells after becoming activated, CTLA-4. In malignant melanoma, ipilimumab showed its beneficial effect as compared to a placebo peptide. However, the therapy with this antibody harbors significant toxicity. Meanwhile, other targets such as PD-1, also expressed on (late) activated T cells, were identified, and therapies with antibodies inhibiting PD-1/PD-L1 are less toxic. Although these antibodies show response only in a minority of patients, the benefit seems durable in some of these patients. In solid tumors such as melanoma or non-small cell lung cancer (NSCLC), treatment with PD-1 inhibitors has resulted in a significant prolongation of survival, even in first-line treatment. As these drugs have been approved in many indications, it is important to know the drugs and side effects. Resistance towards these drugs are caused by low expression of the natural ligand, PD-L1, in the tumor tissue, as well as acquired loss of signal transduction of interferon-related genes such as JAK1 or JAK2, respectively. Also new in cancer therapy are bispecific T cell engager monoclonal antibodies (BiTEs) such as blinatumomab, and autologous chimeric antigen receptor-modified T cells (CAR-Ts). The later have proven their efficacy mainly in hematological neoplasias such as precursor-B-ALL. The dramatic costs of all these new drugs will have an enormous impact on the health care systems in the near future.

• Neubauer, A.