Cutting edge: persistence of transferred lymphocyte clonotypes correlates with cancer regression in patients receiving cell transfer therapy.
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.
Robbins
Paul F
PF
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Paul_Robbins@nih.gov
Dudley
Mark E
ME
Wunderlich
John
J
El-Gamil
Mona
M
Li
Yong F
YF
Zhou
Juhua
J
Huang
Jianping
J
Powell
Daniel J
DJ
Rosenberg
Steven A
SA
D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000008:administration & dosage / Q000032:analysis / Q000235:genetics; D016219:Immunotherapy, Adoptive / Q000379:methods; D018655:Lymphocyte Count; D017710:Lymphocyte Transfusion / Q000379:methods; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D008545:Melanoma / Q000276:immunology* / Q000556:secondary / Q000628:therapy*; D010865:Pilot Projects; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000008:administration & dosage / Q000032:analysis / Q000235:genetics
D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta