Regression of established mouse leukemia by GM-CSF-Transduced tumor vaccine: Implications for cytotoxic T lymphocyte responses and tumor burdens

Chia Ling Hsieh, Victory Feig Pang, Ding Shinn Chen, Lih Hwa Hwang

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Abstract

This study investigated the therapeutic effects of granulocyte-macrophage colony-stimulating factor (GMCSF) on a mouse leukemia model. By using a retroviral vector, mouse GM-CSF cDNA was transduced into a highly tumorigenic T leukemia cell line, RL♂ 1. Injection of GM-CSF-secreting RL♂ 1 cells into syngeneic BALB/c mice elicited protective immunity in the animals, which could regress preestablished tumors introduced either by a subcutaneous or in an intravenous route. However, the therapeutic effects were less prominent in the mice inoculated with a large tumor load or in mice treated later. Winn tests further demonstrated that the splenocytes from the late-treated group conferred poorer protective effects in terms of reducing the growth of parental RL♂ 1 cells in naive mice than the splenocytes from the early-treated group. Nonetheless, upon stimulation in vitro, the activity of tumor-specific cytotoxic T lymphocytes (CTL) was comparable in the splenocytes of both groups of mice. Histological analysis also indicated that the CD8+ T cells appeared as early as 3 days following vaccination at the vaccine sites and at the tumor sites in both groups of mice. Above observations implied that the T cells in the animals bearing large tumors appeared to be in a state of suppression or anergy. Systematic histological analyses for 2 weeks provided further insight into various infiltrates at the vaccine sites and at the tumor sites in response to the inoculation of GM-CSF-secreting tumor vaccine.

Original languageEnglish
Pages (from-to)1843-1854
Number of pages12
JournalHuman Gene Therapy
Volume8
Issue number16
Publication statusPublished - 1997
Externally publishedYes

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Cancer Vaccines
Cytotoxic T-Lymphocytes
Granulocyte-Macrophage Colony-Stimulating Factor
Tumor Burden
Leukemia
Therapeutic Uses
Neoplasms
Vaccines
T-Lymphocytes
Immunity
Vaccination
Complementary DNA
Cell Line
Injections
Growth

ASJC Scopus subject areas

  • Genetics

Cite this

Regression of established mouse leukemia by GM-CSF-Transduced tumor vaccine : Implications for cytotoxic T lymphocyte responses and tumor burdens. / Hsieh, Chia Ling; Pang, Victory Feig; Chen, Ding Shinn; Hwang, Lih Hwa.

In: Human Gene Therapy, Vol. 8, No. 16, 1997, p. 1843-1854.

Research output: Contribution to journalArticle

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