International Immunology, Vol. 15, No. 7, pp. 797-805,
July 2003
© 2003 Japanese Society for Immunology
Successful elimination of large established tumors and avoidance of antigen-loss variants by aggressive adoptive T cell immunotherapy
1 Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
Correspondence to: P. M. Allen; E-mail: allen{at}immunology.wustl.edu
Transmitting editor: J. P. Allison
Utilization of ex vivo-expanded epitope-specific cytotoxic T lymphocytes has become a clinical standard in the adoptive immunotherapy of tumors. One of the obstacles faced by T cell-based immunotherapy is the development of tumor immune-escape variants. Using our previously reported CMS5 tumor/DUC18 CD8+ TCR transgenic system, we sought to investigate whether large established tumors can be successfully eliminated before the development of escape variants. Using BALB/c mice that were s.c. transplanted with two tumors that had been growing for 8 days (double 8-day tumors), we assessed the in vivo anti-tumor activity of in vitro peptide-stimulated DUC18 T cells. A single infusion of activated DUC18 T cells showed a modest effect against the double 8-day tumors, whereas two and three administrations led to regression of both tumors within 10 days. However, in some mice, the tumors re-grew 
10 days after the regression. We found these tumors to be antigen-loss variants. These relapsed tumor cells progressively grew in DUC18 transgenic mice and did not express tERK-specific message. When four doses of activated DUC18 T cells were infused, the double 8-day tumors were successfully eliminated and the tumors did not grow out in any mice. Our results demonstrate that mono-specific CD8+ T cells can effectively eliminate large established tumors before the development of antigen-loss variants when a high number of T cells is rapidly administered.
Keywords: CMS5, DUC18, mono-specific T cell, tERK
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