Establishment of adoptive cell therapy with tumor infiltrating lymphocytes for liver and oesophageal cancer

Publication Type:
Conference Proceeding
Annals of Oncology, 2021, 32, (Supplement 3), pp. S197-S198
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Background: Since the finding in 1986 that tumor infiltrating lymphocytes (TILs) were 50-100 times more effective than lymphokine-activated killer cells in killing cancer cells, TILs have attracted great attention in cancer research. Recently (2019) FDA approved LN-145 as a cancer therapy based on autologous tumor-infiltrating lymphocytes, thus reaffirming that TILs have a great potential as an effective cancer treatment. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and effective adaptive cell therapy is lacking. In the present study, we aimed to establish a method for extracting and purifying TILs for effective adoptive therapy for liver cancer and oesophageal cancer. Methods: TILs were isolated by the traditional method of enzyme digestion combined with mechanical treatment for whole HCC tissues. Tissues were surgically removed and soaked in PBS, to remove the surrounding blood clots, fat and necrotic tissue, and further washed with PBS. Purity and Immunophenotype of TIL cultures were examined by flow cytometry. In the expansion stage of liver cancer TILs, anti-CD3 monoclonal antibody and inactivated PBMC from healthy donor as feeder cells (treated with 10μg/ml mitomycin) were added to the culture medium for stimulation. Results: TIL cells can be isolated from all tumor tissue specimens. TILs from liver cancer were obtained through enzyme digestion and direct induction of tissue mass methods. Phenotype analysis of TILs from liver cancer showed that the proportion of CD3+ and CD3+CD8+ cells in TILs separated by enzymatic digestion was 86.7% and 39.4% on day 7 respectively. On day 19 the proportions of CD3+ and CD3+CD8+ cells were 98.5% and 34.0%, respectively. After 19 days of culture, TIL cells (1.0×107) increased to 2.8×109 meaning that there was 280 times expansion in 19 days. Conclusions: Using an enzyme digestion method, we obtained TILs with higher purity from fresh tissues from patients with HCC. These TILs can be readily expanded to adequate volumes for adoptive cell therapy for patients with liver cancer, paving the way toward use of TILs for HCC therapy.
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