Cutting edge: persistence of transferred lymphocyte clonotypes correlates with cancer regression in patients receiving cell transfer therapy

PF Robbins, ME Dudley, J Wunderlich… - The Journal of …, 2004 - journals.aai.org
PF Robbins, ME Dudley, J Wunderlich, M El-Gamil, YF Li, J Zhou, J Huang, DJ Powell…
The Journal of Immunology, 2004journals.aai.org
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 …
Abstract
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 β-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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