Neoplasms, Liver Clinical Trial
Official title:
Study of Cancer Stem Cell Vcccinie That as a Specific Antigen in Metastatic Adenocarcinoma of the Liver
Most studies of cancer stem cells (CSC) involve the inoculation of cells from human tumors into immunosuppressed mice, preventing an assessment on the immunologic interactions and effects of CSCs. In this study, the investigators examined the vaccination effects produced by CSC-enriched populations from histologically distinct murine tumors after their inoculation into different syngeneic immunocompetent hosts. Enriched CSCs were immunogenic and more effective as an antigen source than unselected tumor cells in inducing protective antitumor immunity.Immune sera from CSC-vaccinated hosts contained high levels of IgG which bound to CSCs, resulting in CSC lysis in the presence of complement.CTLs generated from peripheral blood mononuclear cells or splenocytes harvested from CSC-vaccinated hosts were capable of killing CSCs in vitro. Mechanistic investigations established that CSC-primed antibodies and T cells were capable of selective targeting CSCs and conferring anti-tumor immunity.
To assess the feasibility of generating CSC-loaded DC vaccines for clinical use, the
investigators will harvest peripheral blood and tumor specimen from patients with
hepatocellular cancer. The investigators will purify T, B cells and generate DCs from the
PBMCs of the hepatocellular cancer patient.On the other hand, investigators will isolate
ALDHhigh and ALDHlow tumor cells from the tumor specimen of the hepatocellular cancer
patient using a similar protocol as investigators reported .
Aim 1: To demonstrate, in vitro, the relative cellular anti-hepatocellular cancer CSC
immunity induced by hepatocellular cancer CSC-DC primed cytotoxic T cells.
Aim 2: To determine, in vitro, specific binding and lysis of hepatocellular cancer CSCs by
antibodies produced by purified B cells from PBMCs stimulated with hepatocellular cancer
CSC-DC.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment
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