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The Journal of Immunology, 2004, 173: 7125-7130.
Copyright © 2004 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Persistence of Transferred Lymphocyte Clonotypes Correlates with Cancer Regression in Patients Receiving Cell Transfer Therapy

Paul F. Robbins1, Mark E. Dudley, John Wunderlich, Mona El-Gamil, Yong F. Li, Juhua Zhou, Jianping Huang, Daniel J. Powell, Jr. and Steven A. Rosenberg

Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

The lack of persistence of transferred autologous mature lymphocytes in humans has been a major limitation to the application of effective cell transfer therapies. The results of a pilot clinical trial in 13 patients with metastatic melanoma suggested that conditioning with nonmyeloablative chemotherapy before adoptive transfer of activated tumor-reactive T cells enhances tumor regression and increases the overall rates of objective clinical responses. The present report examines the relationship between T cell persistence and tumor regression through analysis of the TCR {beta}-chain V region gene products expressed in samples obtained from 25 patients treated with this protocol. Sequence analysis demonstrated that there was a significant correlation between tumor regression and the degree of persistence in peripheral blood of adoptively transferred T cell clones, suggesting that inadequate T cell persistence may represent a major factor limiting responses to adoptive immunotherapy.




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