Immunotherapy: Current Status

Abstract

Immune evasion has been recognized as one key strategy for cancer survival and progression. In the recent years several approaches have been developed. Besides passive immunotherapies such as adoptive cell transfer, which had shown limited efficacy combined with substantial toxicity, new active immunotherapies have shown encouraging results in early clinical trials. In the area of antigen-dependent immunotherapies various vaccines, either antigen-specific or tumor-/dendritic-cell based have entered phase 3 clinical trials. Whilst not each trial reported a positive outcome important subgroup prompted further prospective research in this field. In the area of antigen-independent immunotherapies monoclonal antibodies, which are targeting inhibitors at checkpoints of immune response activation cascade have yielded promising results first in melanoma but also in non-small cell lung cancer (NSCLC). Besides the anti-CTL 4 antibody ipilimumab that is currently being investigated in combination with chemotherapy in patients with advanced squamous NSCLC and small cell lung cancer, various antibodies targeting the PD-1 receptor or it's ligand PD-L1 have shown encouraging efficacy in pretreated patients with advanced NSCLC. Randomized trials will evaluate the activity of these compounds compared to standard chemotherapy. Identification of predictive biomarkers will be crucial for the optimal use of these therapies. The focus of development currently lies on the assessment of the PD-L1 expression status, which seems to be related to the efficacy of these therapies. Future approaches will contain evaluation of checkpoint inhibitors in early lines of treatment, in combination with targeted therapies as well as in combination with other immunotherapies.