Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site VSports app下载. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely V体育官网. .

Clinical Trial
. 2004 Dec 15;173(12):7125-30.
doi: 10.4049/jimmunol.173.12.7125.

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

Paul F Robbins  1 , Mark E Dudley, John Wunderlich, Mona El-Gamil, Yong F Li, Juhua Zhou, Jianping Huang, Daniel J Powell Jr, Steven A Rosenberg
Affiliations
Clinical Trial

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

Paul F Robbins et al. J Immunol. .

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 VSports手机版. 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. .

PubMed Disclaimer

Figures (V体育平台登录)

FIGURE 1
FIGURE 1
Comparison of TRBV sequencing results with FACS analysis. The percentages of individual rearranged TRBV sequences obtained using 5′ RACE analysis were compared with the results of FACS analysis conducted with specific TRBV Abs. Samples were only analyzed if the appropriate TRBV Ab was available, and TRBV products that were represented at levels below 5% as determined either by TRBV sequence analysis or by Ab staining were excluded from the analysis. The results obtained using these methods were highly correlated using linear regression analysis (R = 0.8975, p < 0.001).
FIGURE 2
FIGURE 2
Comparisons of the persistence of individual T cell clonotypes in responders and nonresponders. The percentages of all persistent T cell clonotypes that were detected in samples of PBMC obtained between 23 and 63 days following adoptive transfer, as determined using TRBV sequence analysis, were plotted for the responding and nonresponding patients. Each point represents a distinct T cell clonotype that was identified in an individual patient sample.
See this image and copyright information in PMC

References

    1. Rosenberg SA, Aebersold PM, Cornetta K, Kasid A, Morgan RA, Moen R, Karson EM, Lotze MT, Yang JC, Topalian SL, et al. Gene transfer into humans: immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med. 1990;323:570. - PubMed
    1. Dudley ME, Wunderlich J, Nishimura MI, Yu D, Yang JC, Topalian SL, Schwartzentruber DJ, Hwu P, Marincola FM, Sherry R, et al. Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma. J Immunother. 2001;24:363. - V体育官网 - PubMed
    1. Yee C, Thompson JA, Byrd D, Riddell SA, Roche P, Celis E, Green-berg PD. Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc Natl Acad Sci USA. 2002;99:16168. - "V体育安卓版" PMC - PubMed
    1. Dudley ME, Wunderlich JR, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry RM, Marincola FM, Leitman SF, Seipp CA, et al. A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma. J Immunother. 2002;25:243. - PMC - PubMed
    1. Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002;298:850. - PMC - PubMed

MeSH terms

Substances