The era of
immunotherapies was unleashed in 2010 with the Food and Drug Administration (FDA) approval of the first therapeutic
vaccine sipuleucel-T as a standard treatment for metastatic
prostate cancer. Next, the first immune-activating anticytotoxic lymphocyte antigen-4 (CTLA-4) antibody
ipilimumab exhibiting '
immune checkpoint blockade' was approved by FDA and European Medical Agency (EMA) for the treatment of patients with metastatic
melanoma. New generations of immune checkpoint blockading
antibodies targeting programmed cell death 1 (PD-1) and its
ligand (PD-L1) are now under intense investigation in metastatic
melanoma (MM) and
non-small-cell lung cancer (NSCLC), and impressive clinical results are anticipated. Despite these successes, only a fraction of patients become clinical responders to
therapy. Thus, to improve the selection of patients likely to respond, scrutinizing different immune parameters during treatment is essential. In the summary of this PhD thesis, we investigated changes in immune parameters and their possible correlation with clinical efficacy in patients with MM during treatments with the standard chemo- and
immunotherapies,
temozolomide (TMZ) and
interferon-α2b/
interleukin-2 (IFN-α/IL-2)
immunotherapy. The overall aim was to assess changes in frequency and absolute counts of different immune cell subsets before and
after treatment and correlate to clinical benefit. Furthermore, the thesis covers a finalized, clinical phase 1 study in patients with NSCLC testing a
peptide vaccination with a HLA-A2-restricted
epitope derived from
indoleamine 2,3 dioxygenase (IDO). The overall aim in this trial was to evaluate safety and tolerability of IDO as an anticancer
vaccine target in patients with NSCLC and to assess whether immunity correlated to clinical response.