Dendritic cells loaded with CD44+ CT‑26 colon cell lysate evoke potent antitumor immune responses

Abstract

Increasing evidence supports the concept that cancer stem cells (CSCs) are responsible for cancer progression and metastasis, therapy resistance and relapse. In addition to conventional therapies for colon cancer, the development of immunotherapies targeting cancer stem cells appears to be a promising strategy to suppress tumor recurrence and metastasis. In the present study, dendritic cells (DCs) were pulsed with whole-tumor cell lysates or total RNA of CD44+ colon cancer stem cells (CCSCs) isolated from mouse colon adenocarcinoma CT-26 cell cultures and investigated for their antitumor immunity against CCSCs in vivo and in vitro. In a model of colon adenocarcinoma using BALB/c mice, a sequential reduction in tumor volume and weight was associated with an extended survival in tumor-bearing mice vaccinated with DCs pulsed with RNA or CCSC lysate. In addition, a lactate dehydrogenase assay indicated that cytotoxic T-cells derived from the treated mice exhibited strong cytotoxic activity. Additionally, an enzyme-linked immunosorbent assay revealed that the cytotoxic T-cells of the treated mice released higher levels of interferon-γ against CCSCs compared with those of the control group. In all experiments, the antitumor efficacy of the lysate-pulsed DC-treated and RNA-pulsed DC-treated groups were significantly higher compared with that of the DC-treated and control groups. The results of the present study indicated the potential use of DCs pulsed with cancer stem cell lysates as a potent therapeutic antigen to target CSCs in colon cancer. Additionally, the results provided a rationale for using lysate-pulsed DCs in vivo to eliminate residual tumor deposits in post-operative patients.

Efficacy of atovaquone on EpCAM⁺CD44⁺ HCT‑116 human colon cancer stem cells under hypoxia

“…Magnetic-activated cell sorting and FACS. EpCAM + CD44 + HCT-116 cells were obtained by magnetic-activated cell sorting as previously described (24). In brief, dissociated HCT-116 colon cancer cells were labeled with biotin-conjugated EpCAM antibodies (1:50; cat.…”

RNAi mediated silencing of Nanog expression suppresses the growth of human colorectal cancer stem cells

“…Animals A total of 35 6-week-old female athymic BALB/c nude mice (20±2 g) were purchased from Beijing HFK Bioscience Co., Ltd. and housed in the Laboratory Animal Center at Jilin University. All animals bred in speci c pathogen-free conditions, with 25±2℃ temperature, 55±5% humidity and a 12-h light/ dark cycle as the same conditions previously described [22]. Animals had ad libitum access to water and mouse chow diet.…”

“…For survival analysis, mice were sacri ced when tumors measured > 2000 mm 3 or the tumor diameter exceeded 2.0 cm. All of the treatments with mice are according to the protocol of the Animal Care Committee of Jilin University as previously described [22].…”

RNAi mediated silencing of Nanog expression suppresses the growth of human colorectal cancer stem cells

“…A total of 35 6-week-old female athymic BALB/c nude mice (20±2 g) were purchased from Beijing HFK Bioscience Co., Ltd. and housed in the Laboratory Animal Center at Jilin University. All animals bred in speci c pathogen-free conditions, with 25±2℃ temperature, 55±5% humidity and a 12-h light/ dark cycle as the same conditions previously described [20]. Animals had ad libitum access to water and mouse chow diet.…”

“…For survival analysis, mice were sacri ced when tumors measured > 2000 mm 3 or the tumor diameter exceeded 2.0 cm. All of the treatments with mice are according to the protocol of the Animal Care Committee of Jilin University as previously described [20].…”