TY - JOUR
T1 - Generation and assessment of cytokine-induced killer cells for the treatment of colorectal cancer liver metastases
AU - Li, Celine Man Ying
AU - Tomita, Yoko
AU - Dhakal, Bimala
AU - Tin, Teresa
AU - Li, Runhao
AU - Wright, Josephine A.
AU - Vrbanac, Laura
AU - Woods, Susan L.
AU - Drew, Paul
AU - Price, Timothy
AU - Smith, Eric
AU - Maddern, Guy J.
AU - Fenix, Kevin
N1 - Funding Information:
Open Access funding enabled and organized by CAUL and its Member Institutions. This work was supported by a Tour de Cure Early Career Research Grant, an Adelaide Medical School Mature Grant Development Award and Cancer Council SA Beat Cancer Project Grant (K.F.). C.L. was supported by a University of Adelaide Postgraduate Research Scholarship.
Publisher Copyright:
© 2024, The Author(s).
PY - 2024/1
Y1 - 2024/1
N2 - Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Cytokine-induced killer (CIK) cells are an adoptive immunotherapy reported to have strong anti-tumour activity across a range of cancers. They are a heterogeneous mix of lymphoid cells generated by culturing human peripheral blood mononuclear cells with cytokines and monoclonal antibodies in vitro. In this study, we investigated the yield and function of CIK cells generated from patients with CRC liver metastases. We first showed that CIK cells generated in serum free medium X-VIVO 15 were comparable to those from RPMI medium with 10% FBS in terms of the number and percentages of the main subsets of cells in the CIK culture, and the intracellular levels of granzyme B and perforin, and the pro-inflammatory cytokines IL-2, IFN-γ and TNF-α. The CIK cells were cytotoxic to CRC cell lines grown in 2D cultures or as spheroids, and against autologous patient-derived tumour organoids. Donor attributes such as age, sex, or prior chemotherapy exposure had no significant impact on CIK cell numbers or function. These results suggest that functional CIK cells can be generated from patients with CRC liver metastatic disease, and support further investigations into the therapeutic application of autologous CIK cells in the management of patients with CRC liver metastases.
AB - Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Cytokine-induced killer (CIK) cells are an adoptive immunotherapy reported to have strong anti-tumour activity across a range of cancers. They are a heterogeneous mix of lymphoid cells generated by culturing human peripheral blood mononuclear cells with cytokines and monoclonal antibodies in vitro. In this study, we investigated the yield and function of CIK cells generated from patients with CRC liver metastases. We first showed that CIK cells generated in serum free medium X-VIVO 15 were comparable to those from RPMI medium with 10% FBS in terms of the number and percentages of the main subsets of cells in the CIK culture, and the intracellular levels of granzyme B and perforin, and the pro-inflammatory cytokines IL-2, IFN-γ and TNF-α. The CIK cells were cytotoxic to CRC cell lines grown in 2D cultures or as spheroids, and against autologous patient-derived tumour organoids. Donor attributes such as age, sex, or prior chemotherapy exposure had no significant impact on CIK cell numbers or function. These results suggest that functional CIK cells can be generated from patients with CRC liver metastatic disease, and support further investigations into the therapeutic application of autologous CIK cells in the management of patients with CRC liver metastases.
KW - Colorectal cancer
KW - Cytokine-induced killer cells
KW - Liver metastases
KW - Patient-derived tumour organoids
UR - http://www.scopus.com/inward/record.url?scp=85182435970&partnerID=8YFLogxK
U2 - 10.1007/s00262-023-03591-4
DO - 10.1007/s00262-023-03591-4
M3 - Article
AN - SCOPUS:85182435970
SN - 0340-7004
VL - 73
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 1
M1 - 6
ER -