OBJECTIVE: Colorectal cancer (CRC) is one of the most common malignancies in the western world. More than 60% among patients will develop liver metastases. Although surgical resection is the first choice worldwide, at this point an effective approach for the treatment of patients with liver metastasis and cancer recurrence postoperation has not yet been found. The aim of this study is to investigate the role of the allogeneic dendritomas from fusion of DCs and metastatic colon cancer cells in the activation of anti-tumor immunity against colorectal cancer liver metastases. MATERIAL AND METHODS: Hybrids were generated by fused allogeneic human peripheral blood dendritic cells with metastatic colon cancer SW620 cells using 50% polyethylene glycol (PEG). Induction of immune responses was assessed by ex vivo ELISPOT assays. A murine model of CRC liver metastasis was used by intrasplenic injection. The validity of the vaccine was observed by Vaccination CRC liver metastasis murine model with DC/tumor hybrids. RESULTS: The hybrids highly express the major molecules of DCs and tumor cells. The number of hybrids pulsed CTL secreting IFN-gamma was significantly higher when compared to the DC controls (p < 0.01). In a therapeutic setting mice vaccinated with in vitro cultured hybrids produced strong cellular immune responses and significant inhibition of tumor growth, compared to sham vaccinated controls. CONCLUSIONS: Vaccination with hybrids can induces strong cellular responses and significant protection from challenge in SCID mouse metastatic CRC model.
OBJECTIVE:Colorectal cancer (CRC) is one of the most common malignancies in the western world. More than 60% among patients will develop liver metastases. Although surgical resection is the first choice worldwide, at this point an effective approach for the treatment of patients with liver metastasis and cancer recurrence postoperation has not yet been found. The aim of this study is to investigate the role of the allogeneic dendritomas from fusion of DCs and metastatic colon cancer cells in the activation of anti-tumor immunity against colorectal cancer liver metastases. MATERIAL AND METHODS: Hybrids were generated by fused allogeneic human peripheral blood dendritic cells with metastatic colon cancer SW620 cells using 50% polyethylene glycol (PEG). Induction of immune responses was assessed by ex vivo ELISPOT assays. A murine model of CRC liver metastasis was used by intrasplenic injection. The validity of the vaccine was observed by Vaccination CRC liver metastasis murine model with DC/tumor hybrids. RESULTS: The hybrids highly express the major molecules of DCs and tumor cells. The number of hybrids pulsed CTL secreting IFN-gamma was significantly higher when compared to the DC controls (p < 0.01). In a therapeutic setting mice vaccinated with in vitro cultured hybrids produced strong cellular immune responses and significant inhibition of tumor growth, compared to sham vaccinated controls. CONCLUSIONS: Vaccination with hybrids can induces strong cellular responses and significant protection from challenge in SCIDmouse metastatic CRC model.
Authors: Raghav Chandra; John D Karalis; Charles Liu; Gilbert Z Murimwa; Josiah Voth Park; Christopher A Heid; Scott I Reznik; Emina Huang; John D Minna; Rolf A Brekken Journal: Cancers (Basel) Date: 2021-12-09 Impact factor: 6.639