Cell-based Immunotherapy for Colorectal Cancer with Cytokine-induced Killer Cells

Abstract

Colorectal cancer is the third leading cancer worldwide. Although incidence and mortality of colorectal cancer are gradually decreasing in the US, patients with metastatic colorectal cancer have poor prognosis with an estimated 5-year survival rate of less than 10%. Over the past decade, advances in combination chemotherapy regimens for colorectal cancer have led to significant improvement in progression-free and overall survival. However, patients with metastatic disease gain little clinical benefit from conventional therapy, which is associated with grade 3~4 toxicity with negative effects on quality of life. In previous clinical studies, cell-based immunotherapy using dendritic cell vaccines and sentinel lymph node T cell therapy showed promising therapeutic results for metastatic colorectal cancer. In our preclinical and previous clinical studies, cytokine-induced killer (CIK) cells treatment for colorectal cancer showed favorable responses without toxicities. Here, we review current treatment options for colorectal cancer and summarize available clinical studies utilizing cell-based immunotherapy. Based on these studies, we recommend the use CIK cell therapy as a promising therapeutic strategy for patients with metastatic colorectal cancer.

Efficacy of adjuvant cytokine-induced killer cell immunotherapy in patients with colorectal cancer after radical resection

“…Preclinical studies have shown that CIK cells possess cytotoxic activities against different solid tumors, 25 including colorectal cancer. 29 Mechanism analysis found that CIK cell cytotoxicity is mediated by releasing perforin and granzyme granules and dependent on several activating receptors such as NKG2D, NKp30, NKp44, NKp46 and DNAM-1. 25 Thus, the clinical benefit of CIK cells may be due to the direct tumor killing activity in a MHC-independent way, 30 which is different from chemotherapeutic cytotoxic drugs.…”

Application of the chemokine‑chemokine receptor axis increases the tumor‑targeted migration ability of cytokine‑induced killer cells in patients with colorectal cancer

“…Most patients with CRC are already in the late stage at the time of diagnosis and because late-stage tumor cells have already spread or metastasized in patients with late-stage CRC, conventional surgery have little therapeutic benefit. In addition, patients may not be able to tolerate traditional radio-or chemotherapy; therefore, CIK cell treatment may improve the quality of life of these middle-to late-stage patients and extend patient survival time (17,18). In the clinic, however, patients with CRC who have received CIK cell treatment usually present with different clinic efficacies, whereas a number of patients do not experience any therapeutic benefit (3).…”

Cytokine-induced killer cells/dendritic cells-cytokine induced killer cells immunotherapy combined with chemotherapy for treatment of colorectal cancer in China: a meta-analysis of 29 trials involving 2,610 patients

“…Colorectal cancer (CRC) is currently the third common malignant tumor [ 1 , 2 ]. In recent years, CRC incidence in newly developed or economically transitional countries have been significantly raised, and the 5-year survival rate of IV stage CRC patients is lower than 10% [ 2 ]. Surgery, radiotherapy and chemotherapy are the most widely used therapeutic methods for CRC [ 2 ], but their curative effects on CRC patients were poor.…”

“…In recent years, CRC incidence in newly developed or economically transitional countries have been significantly raised, and the 5-year survival rate of IV stage CRC patients is lower than 10% [ 2 ]. Surgery, radiotherapy and chemotherapy are the most widely used therapeutic methods for CRC [ 2 ], but their curative effects on CRC patients were poor. Researchers found these methods were not able to thoroughly remove small lesions and metastatic cells, which raises the probability of cancer recurrence [ 3 ].…”