Short summary

Adoptive T-cell therapy (ACT) based on autologous Tumor-Infiltrating Lymphocytes (TILs) takes advantage of tumor-reactive T-cells naturally present in the tumor lesions and has shown overall response rates of around 50% in metastatic melanoma. Clinical responses in other epithelial cancers has also recently been reported, however with contradicting results

Rationale

It has been suggested, that limited clinical effects could be due to possible inhibition of the TILs by immune checkpoints, such as programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expressed on the T-cell surface, which can be blocked by checkpoint inhibitors such as ipilimumab (anti-CTLA-4) or nivolumab and pembrolizumab (both anti-PD-1).

The rationale and aim of this study is to investigate whether the manufacturing proces of TIL products can be optimised by adding different immune stimulators to the first proces step. Will this new proces be able to generate an sufficient amount of tumor-reactive immune cells and a reduction of the processing time?

Could any immunohistochemical marker anticipate the feasibility of generating good TIL products in the individual patient sample?

Description of the cohort

Our cohort consists of a total of 40 patients diagnosed with either primary Renal Cell Carcinoma, primary high grade serous adenocarcinoma of the ovary, or primary adenocarcinoma in either colon or pancreas. We aim at including 10 patients from each subgroup.

Data and biological material

The collected data consists of fresh tumor tissue sampled from tumors in kidneys, colon, ovaries, and pancreas. Furthermore specific data from the patient journal regarding metastatic status, treatment, date of initial diagnosis, age and gender.

Collaborating researchers and departments

CBio A/S, Søborg

Department of Clinical Gynecology, OUH

Department of Clinical Urology, OUH

Kirurgisk Afdeling A, OUH

Publications associated with the project

Friese C et al. CTLA-4 blockade boosts the expansion of tumor-reaktive CD8+ tumorinfiltrating lymphocytes in ovarian cancer. Sci Rep 2020.Mar 3;10(1):3914. doi: 10.1038/s41598-020-60738-4.