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Generation of a Novel Dendritic-cell Vaccine Using Melanoma and Squamous Cancer Stem Cells
Authors:Qiao Li  Lin Lu  Huimin Tao  Carolyn Xue  Seagal Teitz-Tennenbaum  John H. Owen  Jeffrey S Moyer  Mark E.P. Prince  Alfred E. Chang  Max S. Wicha
Affiliation:1.Department of Surgery, University of Michigan;2.Department of Internal Medicine, University of Michigan;3.Department of Otolaryngology, University of Michigan
Abstract:We identified cancer stem cell (CSC)-enriched populations from murine melanoma D5 syngeneic to C57BL/6 mice and the squamous cancer SCC7 syngeneic to C3H mice using ALDEFLUOR/ALDH as a marker, and tested their immunogenicity using the cell lysate as a source of antigens to pulse dendritic cells (DCs). DCs pulsed with ALDHhigh CSC lysates induced significantly higher protective antitumor immunity than DCs pulsed with the lysates of unsorted whole tumor cell lysates in both models and in a lung metastasis setting and a s.c. tumor growth setting, respectively. This phenomenon was due to CSC vaccine-induced humoral as well as cellular anti-CSC responses. In particular, splenocytes isolated from the host subjected to CSC-DC vaccine produced significantly higher amount of IFNγ and GM-CSF than splenocytes isolated from the host subjected to unsorted tumor cell lysate pulsed-DC vaccine. These results support the efforts to develop an autologous CSC-based therapeutic vaccine for clinical use in an adjuvant setting.
Keywords:Cancer Biology   Issue 83   Cancer stem cell (CSC)   Dendritic cells (DC)   Vaccine   Cancer immunotherapy   antitumor immunity   aldehyde dehydrogenase
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