The Chinese-German Journal of Clinical Oncology

, Volume 2, Issue 4, pp 196–202

Fixed-tumor vaccine: A practical formulation with cytokine-microspheres for protective and therapeutic antitumor immunity

  • Peng Baogang
  • Liang Lijian
  • Liu Shuqin
  • Huang Jiefu
  • He Qiang
  • Lu Mingde
  • Leong Kam W
  • Ohno Tadao
Original Articles

Abstract

Objective: To study the protective and therapeutic antitumor immunity against hepatocellular carcinoma (HCC) with the fixed-tumor vaccine.Methods: A tumor vaccine consisting of fixed tumor cells or fixed tumor fragments combined with sustained-releasers of cytokines and a non-toxic adjuvant was developed. C57BL/6J mice were immunized intra-dermally with the vaccine on day 0 and 7, followed by intrahepatic challenge with live Hepa 1–6 cells.Results: All of 15 nonimmunized control mice developed the hepatoma. Protection of mice immunized with fixed Hepa 1–6 cells and both of IL-2/GM-CSF microspheres or further mixed with TiterMax Gold reached 80% and 87%, respectively. Mass growth of the established tumors, vaccinated twice at 5 mm in diameter, the tumor of control animals continued to grow. However, 7–10 days after the second injection of the tumor vaccine, the tumor growth was suppressed in 9 of 10 mice and then markedly reduced. Complete tumor regression was observed in 60% (6/10) of mice. Splenocytes from the control mice were not able to lyse target Hepa 1–6 cells and other tumor cells. In contrast splenocytes from the vaccinated mice exhibited a 41% lytic activity against the Hepa 1–6 cells tested at an effector/target (E/T) ratio of 5, whereas they did not exhibited such activity against the melanoma cells (B16-F1), Lewis lung carcinoma cells (LLC), renal carcinoma cells (Renca), and bladder carcinoma cells (MBT-2). The cytotoxic activity was inhibited by the treatment with anti-CD3, anti-CD8, and anti-MHC-class I monoclonal antibodies but not with anti-CD4 and anti-MHC-class II antibodies. In the Phase-I clinical trial, vaccination of HCC patients with the autologous vaccine is a well-tolerated treatment and induces fixed tumor fragment-specific immunity.Conclusion: Fixed HCC vaccination elicited protective and therapeutic antitumor immunity against HCC. The tumor vaccine elicited antigen specific CTL response lysis of the target HCC was mediated by the typical MHC-class I restricted CD8+ T cells.

Key words

cancer vaccine cytotoxic T lymphocyte immunotherapy hepatoma 

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Copyright information

© Springer 2003

Authors and Affiliations

  • Peng Baogang
    • 1
    • 2
  • Liang Lijian
    • 1
  • Liu Shuqin
    • 3
  • Huang Jiefu
    • 1
  • He Qiang
    • 1
  • Lu Mingde
    • 1
  • Leong Kam W
    • 3
  • Ohno Tadao
    • 2
  1. 1.Department of Hepatobiliary SurgeryFirst Affiliated Hospital of Sun Yat-Sen University of Medical ScienceGuangzhouChina
  2. 2.Riken Cell BankRiken (The Institute of Physical and Chemical Research)Tsukuba Science City, IbarakiJapan
  3. 3.Department of Biomedical Engineering, School of MedicineJohns Hopkins UniversityBaltimore

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