Preventive Cancer Stem Cell-Based Vaccination Reduces Liver Metastasis Development in a Rat Colon Carcinoma Syngeneic Model

Abstract

Cancer stem cells (CSCs) represent a minor population of self-renewing cancer cells that fuel tumor growth. As CSCs are generally spared by conventional treatments, this population is likely to be responsible for relapses that are observed in most cancers. In this work, we analyzed the preventive efficiency of a CSC-based vaccine on the development of liver metastasis from colon cancer in a syngeneic rat model. We isolated a CSC-enriched population from the rat PROb colon carcinoma cell line on the basis of the expression of the aldehyde dehydrogenase-1 (ALDH1) marker. Comparative analysis of vaccines containing lysates of PROb or ALDH high cells by mass spectrometry identifies four proteins specifically expressed in the CSC subpopulation. The expression of two of them (heat shock protein 27-kDa and aldose reductase) is already known to be associated with treatment resistance and poor prognosis in colon cancer. Preventive intraperitoneal administration of vaccines was then performed before the intrahepatic injection of PROb cancer cells. While no significant difference in tumor occurrence was observed between control and PROb-vaccinated groups, 50% of the CSC-based vaccinated animals became resistant to tumor development. In addition, CSC-based vaccination induced a 99.5% reduction in tumor volume compared to the control group. To our knowledge, this study constitutes the first work analyzing the potential of a CSC-based vaccination to prevent liver metastasis development. Our data demonstrate that a CSCbased vaccine reduces efficiently both tumor volume and occurrence in a rat colon carcinoma syngeneic model.

Targeting head and neck tumoral stem cells: From biological aspects to therapeutic perspectives

“…Studies showed that cytotoxic T lymphocytes generated from peripheral blood mononuclear cells or splenocytes harvested from CSCvaccinated hosts had the ability to kill CSCs in vitro [42] . Consistent with the findings of Ning group, Duarte et al [43] first demonstrated an ALDH(high)…”

Cancer stem cell vaccine inhibits metastases of primary tumors and induces humoral immune responses against cancer stem cells

“…[37][38][39][40] However, the mechanisms involved have yet to be fully defined and no experimental evidence has been provided for direct targeting of CSCs by CSC-DC vaccine-induced anti-CSC immunity. We report herein that the therapeutic efficacy of our CSC-DC vaccine was associated with significantly inhibited metastasis to the lung.…”

Immunologic Approaches to Targeting Cancer Stem Cells

“…Among these proteins, two of them (heat shock protein 27-kDa and aldose reductase) are already known to be associated with treatment resistance and poor prognosis in colon cancer. They then inoculated rats with the cancer stem cell lysate (not purifi ed antigens) as vaccine and found that the cancer stem cell-based vaccine reduced tumor volume and occurrence and inhibited experimental liver metastasis in half of the animals [ 78 ]. This report provides evidence for the existence of cancer stem cell-associated antigens in the lysate used to prime DCs.…”

“…Experimental evidence has demonstrated that cancer stem cell-DC vaccines confer animal host antitumor immunity by direct targeting of cancer stem cells by antibody and CTLs [ 77 ], but the molecule(s) responsible for such cancer stem cell-conferred antitumor activity remain unknown. In this regard, Duarte et al used mass spectrometry to compare protein expression difference between cancer stem cells and non-cancer stem cells in colon carcinoma and identifi ed four proteins specifi cally expressed in the cancer stem cells [ 78 ]. Among these proteins, two of them (heat shock protein 27-kDa and aldose reductase) are already known to be associated with treatment resistance and poor prognosis in colon cancer.…”