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Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Cellular Vaccines Modified with Hyper IL6 or Hyper IL11 Combined with Docetaxel in an Orthotopic Prostate Cancer
Jacek Mackiewicz1, Urszula Kazimierczak2, Marek Kotlarski2
1Medical Biotechnology, University of Medical Sciences, Poznan, Poland Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland Department of Medical and Experimental Oncology, Clinical Hospital of Poznan University of Medical Sciences, Poznan, Poland jmackiewicz@ump.edu.pl.
Background:
Whole-cell-based vaccines modified with Hyper-IL-6 (H6) and Hyper-IL-11 (H11) have demonstrated high activity in murine melanoma and renal cancer models.
Materials And Methods:
H6 and H11 cDNA was transduced into TRAMP cells (TRAMP-H6 and TRAMP-H11). An orthotopic TRAMP model was employed. The efficacy of TRAMP-H6 and TRAMP-H11 in combination with docetaxel was evaluated. Immune cells infiltrating tumors were assessed.
Results:
Immunization with TRAMP-H6 and TRAMP-H11 vaccines extended OS of mice. Addition of docetaxel to TRAMP-H6 and TRAMP-H11 vaccines further extended OS of the animals. Vaccination with TRAMP-H6 alone and TRAMP-H11 combined with docetaxel augmented tumor infiltration by activated CD8(+) and CD4(+) T-cells and attracted higher number of activated, mature DCs infiltrating tumors. Addition of docetaxel to TRAMP-H6, TRAMP-H11, TRAMP-Adv700 vaccines enhanced the infiltration of the tumor by NK cells.
Conclusion:
Addition of docetaxel to modified TRAMP vaccines improved clinical benefit of treated mice and enhanced anti-tumor immune response.
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