This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cheever, M. A. Articles by Fefer, A. Search for Related Content PubMed PubMed Citation Articles by Cheever, M. A. Articles by Fefer, A.

Adoptive Therapy of Established Syngeneic Leukemia by Cells Primarily Sensitized in Vitro¹

Division of Oncology, Department of Medicine, University of Washington School of Medicine, and the Fred Hutchinson Cancer Research Center, Seattle, Washington 98195

The aim of the current studies was to determine whether cells primarily sensitized in vitro are effective in adoptive therapy of established tumors. Spleen cells from normal BALB/c mice were cultured for 5 days at variable responder:stimulator ratios with an X-irradiated syngeneic Moloney virus-induced leukemia (LSTRA), denoted as BALB/c·(LSTRA)_x, or with X-irradiated normal BALB/c spleen cells, denoted as BALB/c·(BALB/c)_x, and tested for ability to eradicate an established lethal inoculum of LSTRA in adoptive chemoimmunotherapy.

BALB/c mice inoculated with 2 x 10³ LSTRA i.p. on Day 0 were treated on Day 5 with cyclophosphamide (180 mg/kg) plus 1 x 10⁷ cultured cells. Treatment with cyclophosphamide alone cured only 3% of mice. As an adjunct to cyclophosphamide, therapy with BALB/c·(BALB/c)_x cultured at responder:stimulator ratios of 8:1, 32:1, and 128:1 cured 29%, 37%, and 33% of mice, respectively; and BALB/c·(LSTRA)_x cultured at the same responder:stimulator ratios cured 54, 83, and 29% of mice, respectively. Furthermore, the therapeutic efficacy of BALB/c·(LSTRA)_x was abrogated by treatment with anti-Thy 1.2 + complement. Thus, culture of normal lymphoid cells with tumor at optimal responder:stimulator ratios substantially enhanced their ability to eradicate established tumor, and the enhanced therapeutic efficacy was mediated by a T-cell generated during culture.

The specificity of primary in vitro sensitization in generating cells effective in the therapy of established tumors was confirmed by treating BALB/c^H-2d x C57BL/6^H-2b F₁ (hereafter called B6F₁) mice bearing either LSTRA^H-2d or an antigenically distinct chemically induced leukemia, EL-4(G-)^H-2b, with CB6F₁ spleen cells sensitized in vitro to either of the parental tumors.

¹ This work was supported by Grant CA 10777 and Contract N01-CB-84247 from the National Cancer Institute, NIH.

² To whom requests for reprints should be addressed.

³ American Cancer Society Junior Faculty Fellow.

⁴ American Cancer Society Professor of Clinical Oncology.

Received 9/25/80. Accepted 4/ 2/81.

This article has been cited by other articles:

				O. J. Finn Cancer Immunology N. Engl. J. Med., June 19, 2008; 358(25): 2704 - 2715. [Full Text] [PDF]

				C. H. Poehlein, H.-M. Hu, J. Yamada, I. Assmann, W. G. Alvord, W. J. Urba, and B. A. Fox TNF Plays an Essential Role in Tumor Regression after Adoptive Transfer of Perforin/IFN-{gamma} Double Knockout Effector T Cells J. Immunol., February 15, 2003; 170(4): 2004 - 2013. [Abstract] [Full Text] [PDF]