The rigorous evaluation of cancer therapeutics requires a real and quantifiable evidence of benefit to patients with cancer (42). Clinical trials are expensive and require considerable human and clinical resources in order to demonstrate this benefit. In the case of immunotherapy, identification of defined cancer antigens will allow to evaluate immunogenic targets, and assess the quality and magnitude of immune responses against these antigens following therapeutic intervention. Within the IMMOMEC consortium we could recently demonstrate that the clinical outcome from a peptide vaccination in melanoma patients could be predicted by the extend of the vaccination-induced T cell response revealing this parameter as a surrogate marker for the clinical benefit. Analyzing such surrogate endpoints within a clinical trial complements clinical assessments like tumor response. Finally, it will provide a tool to predict a patient’s clinical course during specific treatment in a depth of understanding beyond that of current possibilities.
Immunomonitoring of a vaccination therapy in melanoma. Vaccination-induced CD8+ T cells recognize modified and wild type HLA-A2-restricted survivin epitopes. Cells were stained with HLA-multimers A*0201-ILKEPVHGV-PE plus A*0201-LTLGEFLKL-APC (wildtype epitope) (A) or with HLA-multimers A*0201-LMLGEFLKL-PE (modified epitope) plus A*0201-ILKEPVHGV-APC (B). Survivin-specific T cell reactivities of the per-protocol melanoma patient population (55 patients) diagramed by (C) vaccination regimens; (D) patients’ HLA type; (E) best overall response grouped as progression arrest (CR+PR+SD) and progression (PD); and (F) inflammatory reaction at the vaccination sites. Patients demonstrating a positive detection of survivin-specific T cell reactivity were defined positive (green bars); patients without any positive reactivity throughout the vaccination period were considered as negative (red bars). Fisher’s exact test was used to compare T cell reactivities between groups; p-values are provided above the corresponding bars.