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Specific adoptive immunotherapy of malignant glioma with long-term cytotoxic T lymphocyte line expanded in T-cell growth factor

Experimental Study and Future Prospects

  • Chemotherapy and immunotherapy of malignant gliomas
  • —A contribution by Japanese Neurosurgery—
  • Published:
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Summary

The purposes of the current study were: (1) to investigate the immunoregulatory effects of T-cell growth factor (TCGF) on the activation and differentiation of syngeneic cytotoxic T lymphocyte (CTL) populations generated against a 20-methylcholanthrene-induced ependymoblastoma, 203-glioma, in C57BL/6 mice; and (2) to determine whether the glioma-specific CTL clone (G-CTLL) could be established by TCGF, and whether thein vivo efficacy of the cloned cells could be rendered more effective in adoptive therapy.

It was found that TCGF largely allows the CTL populations to proliferate and thus can activate the depressed cytotoxic activity in tumour-bearing mice.

Two lines of G-CTLL were successfully obtained by the limiting dilution technique. The G-CTLL retained a TCGF-dependent proliferative growth and a marked cytotoxic activity with target specificity for over 18 months, characterized by a surface phenotype of Lyt-1−·2·3+, Lyt-2 antibody blocking of cytotoxicity and the production of immune interferon in response to mitogen and tumour antigen.

In the Winn assay and the adoptive transfer assay, the therapeutic effects were detected in intracranially inoculated tumours in mice. Thein vivo efficacy was dependent on the dose of G-CTLL and on the time of the intravenous administration, although the transfer was inversely ineffective in conditions of increased intracranial pressure. The mechanism responsible for thein vivo effect was probably due to the adoptive immunity and/or the tumour-specific interferon production of G-CTLL.

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Abbreviations

G-CTLL:

glioma-specific cytotoxic T lymphocyte clone

TCGF:

T-cell growth factor

IFN:

interferon

IL:

interleukin

TSF:

thymocyte stimulating factor

LAF:

lymphocyte activating factor

CTL:

cytotoxic T lymphocyte

Tc:

regional lymph node T-cells(s)

Ts:

splenic T-cell(s)

IICP:

increased intracranial pressure

RPMI:

Roswell Park Memorial Institute

PBS:

phosphate-buffered saline

CM:

conditioned medium

Con A:

concanavalin A

E/T:

effector to target cell ratio

i.c.:

intracranial(ly)

s.c.:

subcutaneous(ly)

i.v.:

intravenous(ly)

ATx:

adult thymectomy

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Authors and Affiliations

  1. Department of Neurosurgery, Kyoto University Medical School, 54-Kawaharocho, Shogoin, Sakgo-Ku, 606, Kyoto, Japan

    Toshiki Yamasaki, Hajime Handa & Junkoh Yamashita

  2. Department of Molecular Biology and Virology Institute for Virus Research, Kyoto University, Japan

    Yoshihiko Watanabe

  3. Department of Pathology, Institute for Virus Research, Kyoto University, Japan

    Yuziro Namba & Masao Hanaoka

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  1. Toshiki Yamasaki
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Yamasaki, T., Handa, H., Yamashita, J. et al. Specific adoptive immunotherapy of malignant glioma with long-term cytotoxic T lymphocyte line expanded in T-cell growth factor. Neurosurg. Rev. 7, 37–54 (1984). https://doi.org/10.1007/BF01743289

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