Background <p>Various forms of cancer immunotherapy are promising in overcoming the obstacles posed by resistance to conventional chemo- and radiotherapy. Cancer vaccines could serve as beneficial adjuncts to conventional therapies, offering the potential for fine-tuning to reduce relapse and related mortality. Continuing prior investigations, a therapeutic colorectal cancer stem cell (CSC)-based vaccine was developed to explore whether this vaccination could inhibit the formation and prolong survival rates in a mouse model of colorectal cancer.</p> Methods <p>CSCs were enriched from the CT-26 cell line using sphere formation assay and characterized by real-time q-PCR for stemness genes (<i>Oct4</i>,<i> Sox2</i>, and <i>Nanog</i>) and tumorigenesis assay in syngeneic BALB/c mice. Different groups of mice were intraperitoneally immunized with the CSC lysate-based vaccine, the parental cell lysate-based vaccine, and control groups following subcutaneous challenge with CT-26 cells. Beyond analyzing tumor growth and survival rates, histological analysis of tumor tissues was conducted using comprehensive hematoxylin and eosin (H&amp;E) staining, and antibody responses in vaccinated mice were evaluated by flow cytometry and immunofluorescence.</p> Results <p>Immunization of tumor-bearing mice with the CT-26 CSC lysate-based vaccine caused delayed tumor formation, reduced tumor growth rate, and enhanced survival rate compared to the control groups. The histological responses observed in the lysate vaccination subgroups indicated a potent immune response. Furthermore, flow cytometry and immunofluorescence analyses demonstrated the production of anti-CSC and anti-parental cell antibodies in mice immunized with CT-26 CSC and parental cell lysates.</p> Conclusion <p>These findings suggest that targeting CSCs using a CSC lysate-based vaccine can stimulate cellular and humoral immunity and represent a novel therapeutic approach to complement conventional antitumor therapies.</p> Graphical abstract <p></p>

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Therapeutic efficacy of cancer stem cell-based vaccine in colorectal murine model: reduced tumor growth and prolonged survival

  • Farideh Hashemi,
  • Masoumeh Dehghan Manshadi,
  • Sadegh Safaei,
  • Hossein Aminianfar,
  • Mahmood Bozorgmehr,
  • Leila Eini,
  • Ahmad Shariftabrizi,
  • Mahdieh Razmi,
  • Marzieh Naseri,
  • Roya Ghods,
  • Zahra Madjd

摘要

Background

Various forms of cancer immunotherapy are promising in overcoming the obstacles posed by resistance to conventional chemo- and radiotherapy. Cancer vaccines could serve as beneficial adjuncts to conventional therapies, offering the potential for fine-tuning to reduce relapse and related mortality. Continuing prior investigations, a therapeutic colorectal cancer stem cell (CSC)-based vaccine was developed to explore whether this vaccination could inhibit the formation and prolong survival rates in a mouse model of colorectal cancer.

Methods

CSCs were enriched from the CT-26 cell line using sphere formation assay and characterized by real-time q-PCR for stemness genes (Oct4, Sox2, and Nanog) and tumorigenesis assay in syngeneic BALB/c mice. Different groups of mice were intraperitoneally immunized with the CSC lysate-based vaccine, the parental cell lysate-based vaccine, and control groups following subcutaneous challenge with CT-26 cells. Beyond analyzing tumor growth and survival rates, histological analysis of tumor tissues was conducted using comprehensive hematoxylin and eosin (H&E) staining, and antibody responses in vaccinated mice were evaluated by flow cytometry and immunofluorescence.

Results

Immunization of tumor-bearing mice with the CT-26 CSC lysate-based vaccine caused delayed tumor formation, reduced tumor growth rate, and enhanced survival rate compared to the control groups. The histological responses observed in the lysate vaccination subgroups indicated a potent immune response. Furthermore, flow cytometry and immunofluorescence analyses demonstrated the production of anti-CSC and anti-parental cell antibodies in mice immunized with CT-26 CSC and parental cell lysates.

Conclusion

These findings suggest that targeting CSCs using a CSC lysate-based vaccine can stimulate cellular and humoral immunity and represent a novel therapeutic approach to complement conventional antitumor therapies.

Graphical abstract