T-cell based immunotherapy in pancreatic cancer - basic concepts and pre-clinical development

Activity Code: FP7-PEOPLE-2013-CIG
Project Reference: 618451
Coordinator:German Cancer Research Center

Description:

Pancreatic ductal adenocarcinoma (PDA) has a devastating prognosis and novel treatment approaches are urgently needed. T cell-based immunotherapy making use of in vitro expanded tumour-infiltrating lymphocytes (TIL) has recently emerged as a potent therapy in melanoma, with the potential to cure even patients with advanced disease.
We are currently working towards the development of TIL therapy for PDA on basis of our following findings:

• Although PDA has been branded poorly immunogenic, we found most tumours contain a rich immune infiltrate that comprises high numbers of T-cells
• Most T-cells display an activated phenotype, while the fraction of CD4+ T-regulatory cells is not higher than that found in peripheral blood of healthy subjects
• TILs from PDA biopsies can readily be cultured and expanded, with the same efficiency as melanoma TILs.

Given these findings, the malignancy of PDA and the high unmet medical need it represents, we strongly feel that TIL therapy could offer the potent, fast-acting treatment approach we are looking for. Our project has two major aims:

• To achieve pre-clinical proof of concept for the anti-tumour action of PDA-derived TILs, as a prelude to clinical application of TIL therapy in this disease.
• To obtain in-depth insight in the character and antigen-specificity of the natural TIL response in PDA

Our effort is part of a multi-disciplinary program on PDA that is based on the availability of large numbers of tumour biopsies from the European Pancreas Center, one of the world’s largest clinical centers for pancreatic surgery (>400 PDA resections yearly). Within this program, samples from each tumour will be used not only for TIL isolation, but also for establishing xenografts, exome sequencing and histological evaluation of tumour biological/immunological biomarkers. The availability of matched xenografts and exome/histology data will allow us to incisively study the functionality of our TIL cultures.