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

• Published in: The Journal of immunology (1950) Vol. 173; no. 12; pp. 7125 - 7130
• Main Authors: Robbins, Paul F, Dudley, Mark E, Wunderlich, John, El-Gamil, Mona, Li, Yong F, Zhou, Juhua, Huang, Jianping, Powell, Daniel J., Jr, Rosenberg, Steven A
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.12.2004
• Subjects: Cell Proliferation; Cell Survival - genetics; Cell Survival - immunology; Clone Cells; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Humans; Immunoglobulin Variable Region - administration & dosage; Immunoglobulin Variable Region - analysis; Immunoglobulin Variable Region - genetics; Immunotherapy, Adoptive - methods; Lymphocyte Count; Lymphocyte Transfusion - methods; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Lymphocytes, Tumor-Infiltrating - pathology; Lymphocytes, Tumor-Infiltrating - transplantation; Melanoma - immunology; Melanoma - secondary; Melanoma - therapy; Pilot Projects; Receptors, Antigen, T-Cell, alpha-beta - administration & dosage; Receptors, Antigen, T-Cell, alpha-beta - analysis; Receptors, Antigen, T-Cell, alpha-beta - genetics
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.12.7125

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.