Generation and assessment of cytokine-induced killer cells for the treatment of colorectal cancer liver metastases

Abstract

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 (PBMCs) with cytokines and monoclonal antibodies in vitro. We compared CIK cells from healthy donors and donors with CRC liver metastases, generated in RPMI supplemented with 10% fetal bovine serum (FBS) or three different serum-free media. 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. There was no significant difference in cytotoxicity against CRC cell lines grown in 2D cultures or as spheroids, and against autologous patient-derived tumour organoids. CIK cells from patients with CRC liver metastases grown in X-VIVO 15 media were similar to those from healthy donors in each of the measures. Donor attributes such as age, sex, or prior chemotherapy exposure had no significant impact on CIK cell numbers or function. These results support further investigations into the therapeutic application of autologous CIK cells in the management of patients with CRC liver metastases.