Preclinical Development of Tumor-Infiltrating Lymphocytes (TILs) based Adoptive Cell Transfer immunotherapy (ACT) for patients with sarcoma

​PhD student: Morten Nielsen, MD​

Sarcomas are a heterogenous group of malignant tumors arising from cells of mesenchymal origin. Soft tissue sarcomas are most frequent, while bone sarcomas, in spite of being less frequent, account for more than 10 % of solid cancers in higher adolescents. The overall incidence of sarcomas in Denmark is approximately 300 per year, in Europe the number is approximately 30.000.

Unresectable or metastatic stages of sarcomas, respond poorly to current treatment, and prognosis are extremely severe. Thus, the need for new and improved treatment is obvious. ACT based on infusion of autologous TILs has demonstrated the ability to induce complete and durable response in some patients with advanced malignant melanoma, and we believe that this approach could also be effective in treating sarcomas. With this preclinical study we are investigating feasibility of expanding TILs from sarcoma, as well as performing functional in vitro analyses on these TILs. 

TILs are extracted from tumor samples from sarcoma patients undergoing standard-of-care surgery. Following this initial expansion, selected TIL cultures are undergoing a rapid expansion (REP) by stimulating with IL-2, OTK-3 and feeder cells. Phenotypic analyses are performed using flowcytometri using a broad panel of flourochrome-conjugated monoclonal antibodies. Reactivity analyses are performed using Elispot and/or flowcytometri against autologous (if available) or allogenic HLA-matched tumor cells.

This project will increase our knowledge of tumor-immune interplay in sarcoma patients with the aim to establish a platform for initiation of a clinical ACT feasibility trial for sarcoma patients in the near future.