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Cytotechnology

, Volume 37, Issue 1, pp 31–40 | Cite as

Assessment of the number of local cytotoxic T lymphocytes required for degradation of micrometer-size tumor spheroids

  • Koji Kawai
  • Hitoshi Hayashi
  • Yoshinobu Ozaki
  • Kaoru Saijo
  • Shu Qin Liu
  • Hideyuki Akaza
  • Tadao OhnoEmail author
Article

Abstract

Adoptive immunotherapy with human cytotoxic T lymphocytes (CTL) is a promising cancer treatment. Previously we showed that human CTLs against various types of tumors can be efficiently produced by coculturing peripheral blood cells with target cells. The aims of this study were to simulate the interaction of CTLs and micrometer-size tumor tissues in vitro and to assess the required number of CTLs at local tumor sites for degradation of a tumor. Allogeneic CTLs against a human transitional cell carcinoma cell line and autologous CTLs against a renal cell carcinoma cell derived from a surgical specimen were generated. The cytotoxic activities of CTLs against tumor cells in monolayer culture and tumor spheroids formed in U-bottom 96-well culture plates were assessed. Both allogeneic and autologous CTLs showed greater destructive activity than lymphokine activated killer (LAK) cells against target tumor spheroids. CTLs inoculated at E/T ratios of 0.1 to 1 coexisted with the tumor spheroid for 5 to 6 days and then increased in number with apparently lethal activity against the tumor spheroid. In contrast to CTLs, the increase in LAK cell numbers was scarcely observed, and the proliferated LAK cells did not show cytotoxicity against the tumor spheroid. These observations suggest that, when a small number of CTLs reach a local tumor site, they can destroy micrometer-size tumors after considerable local proliferation.

adoptive immunotherapy cytotoxic T lymphocyte spheroid three-dimensional culture tumor 

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Koji Kawai
    • 1
    • 2
  • Hitoshi Hayashi
    • 1
    • 2
  • Yoshinobu Ozaki
    • 1
  • Kaoru Saijo
    • 1
  • Shu Qin Liu
    • 1
  • Hideyuki Akaza
    • 2
  • Tadao Ohno
    • 3
    Email author
  1. 1.The Institute of Physical and Chemical Research (RIKEN), KoyadaiRIKEN Cell BankTsukuba Science City, IbarakiJapan
  2. 2.Department of Urology, Institute of Clinical MedicineUniversity of Tsukuba, TennodaiTsukuba Science City, IbarakiJapan
  3. 3.The Institute of Physical and Chemical Research (RIKEN), KoyadaiRIKEN Cell BankTsukuba Science City, IbarakiJapan

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