Complete remission of liver metastasis of pancreatic cancer under vaccination with a HLA-A2 restricted peptide derived from the universal tumor antigen survivin

Abstract

Purpose: As prognosis of advanced pancreatic cancer remains gloomy, novel therapeutic modalities have to be developed. Immunotherapy, which targets tumor-associated antigens of tumor cells or tumor stroma, is currently under investigation. As survivin is expressed by neoplastic and tumor endothelial cells, but rarely by normal cells, this antigen appears as an intriguing target molecule.

Methods: A 72-year old patient, suffering from pancreatic cancer refractory to gemcitabine therapy, received the survivin-based peptide vaccinations consisting of 100 mug of a modified HLA-A2 restricted survivin(96-104) epitope in Montanide(R). Each visit the patient was assessed for adverse events, quality of life and immunological response. Immuno-monitoring was performed by IFN-gamma-ELISPOT analysis of peripheral blood lymphocytes. Clinical outcome was evaluated by repetitive computed tomography.

Results: Under vaccination with survivin peptides the patient initially underwent partial remission of liver metastasis which proceeded after 6 months into a complete remission with a duration of 8 months. Immunological monitoring revealed strong vaccine-induced immune-reactivity against survivin. Unfortunately, after the patient was weaned from vaccination in state of no evidence of disease, he developed recurrent disease.

Conclusion: T-cell responses against survivin-expressing cells of the tumor itself and tumor endothelium should impact tumor growth and metastasis. The presented patient with pancreatic cancer is the first example of a successful application of a survivin-based vaccination in the clinical setting. An ongoing phase I/II trial with HLA-A1, -A2 and -B35 restricted survivin peptides for patients with advanced cancer will provide further information towards this notion.

Fig. 1

a Hematoxylin–eosin stain, showing a diffuse infiltration of a mucinous carcinoma. b Immunhistochemical stain of survivin-expressing cells in pancreatic carcinoma. Positive are neoplastic and endothelial cells. c Helical dual-phase, contrast-enhanced CT-scans of the abdomen. Marginal hypodense focus in the liver with enhancement in the early portovenous contrast medium phase. d No remaining sign of liver metastasis

Fig. 2

a Vaccination site of the right thigh. Erythematous, palpable, slightly painful indurations without local hyperthermia. b Immunological monitoring during vaccination therapy with survivin peptide. The IFNγ-ELISPOT analysis of peripheral blood lymphocytes (PBL) shows a significant increase in survivin reactive cells over the time of 6 months