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

Ma, S; Chen, S; Zou, C; An, H; Yin, H; Lin, Y

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

Ma, S Chen, S Zou, C An, H Yin, H Lin, Y

Permalink

Publisher:: Elsevier
Publication Type:: Conference Proceeding
Citation:: Annals of Oncology, 2021, 32, (Supplement 3), pp. S197-S198
Issue Date:: 2021-06-30

Closed Access

	Filename	Description	Size
	P-296 Establishment of adoptive cell therapy with tumor-infiltrating lymphocytes for liver and oesophageal cancer - Annals of Oncology.pdf	Published version	99.74 kB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Closed Access

This item is closed access and not available.

Full metadata record

Field	Value	Language
dc.contributor.author	Ma, S
dc.contributor.author	Chen, S
dc.contributor.author	Zou, C
dc.contributor.author	An, H
dc.contributor.author	Yin, H
dc.contributor.author	Lin, Y https://orcid.org/0000-0002-4637-9701
dc.date	2021-06-30
dc.date.accessioned	2021-07-06T13:36:30Z
dc.date.available	2021-04-16
dc.date.available	2021-07-06T13:36:30Z
dc.date.issued	2021-06-30
dc.identifier.citation	Annals of Oncology, 2021, 32, (Supplement 3), pp. S197-S198
dc.identifier.issn	0923-7534
dc.identifier.uri	http://hdl.handle.net/10453/149842
dc.description.abstract	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.
dc.language	en
dc.publisher	Elsevier
dc.relation.ispartof	Annals of Oncology
dc.relation.ispartof	The 22nd World Congress on Gastrointestinal Cancer
dc.relation.isbasedon	10.1016/j.annonc.2021.05.350
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1112 Oncology and Carcinogenesis
dc.subject.classification	Oncology & Carcinogenesis
dc.title	Establishment of adoptive cell therapy with tumor infiltrating lymphocytes for liver and oesophageal cancer
dc.type	Conference Proceeding
utslib.citation.volume	32
utslib.location.activity	Virtual
utslib.for	1112 Oncology and Carcinogenesis
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access	*
pubs.consider-herdc	true
dc.date.updated	2021-07-06T13:36:29Z
pubs.finish-date	2021-07-03
pubs.issue	Supplement 3
pubs.publication-status	Published
pubs.start-date	2021-06-30
pubs.volume	32
utslib.citation.issue	Supplement 3

Abstract:

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/149842