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Generation of diffuse large B cell lymphoma-associated antigen-specific V?6/V?13+T cells by TCR gene transfer.

ABSTRACT: BACKGROUND: Our previous study had amplified antigen-specific full-length TCR ? and ? genes of clonally expanded T cells in the peripheral blood (PB) of patients with diffuse large B-cell lymphoma (DLBCL). The transfer of T cell receptor (TCR) genes endows T cells with new antigen specificity. Therefore, the aim of this study is to generate diffuse large B cell lymphoma (DLBCL)-specific T cells by T cell receptor (TCR) gene transfer. MATERIALS AND METHODS: Two different eukaryotic expression plasmids harboring TCR V?6 and TCR V?13 genes specific for DLBCL-associated antigens were constructed and subsequently transferred into human T cells using Nucleofector™ technique. The expression of targeted genes in TCR gene-modified cells was detected by real-time PCR, and western blot using TCR V? antibody. The specific cytotoxicity of TCR gene-transferred T cells in vitro was estimated using a lactate dehydrogenase (LDH) release assay. RESULTS: Two different eukaryotic expression plasmids harboring TCR V?6 and TCR V?13 genes specific for DLBCL-associated antigens were constructed and subsequently transferred into T cells from healthy donors. Specific anti-DLBCL cytotoxic T lymphocytes (CTL) could be induced by transduction of specific TCR gene to modify healthy T cells. The transgene cassette of TCR V?13-IRES-TCR V?6 was superior to the other in the function of TCR-redirected T cells. CONCLUSIONS: Specific anti-DLBCL cytotoxic T lymphocyte (CTL) could be inducted by transduction of specific TCR gene to modify healthy T cells.

SUBMITTER: Yin Q

PROVIDER: S-EPMC3024308 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Generation of diffuse large B cell lymphoma-associated antigen-specific Vα6/Vβ13+T cells by TCR gene transfer.

Yin Qingsong Q Zha Xianfeng X Yang Lijian L Chen Shaohua S Zhou Yubing Y Wu Xiuli X Li Yangqiu Y

Journal of hematology & oncology 20110111

<h4>Background</h4>Our previous study had amplified antigen-specific full-length TCR α and β genes of clonally expanded T cells in the peripheral blood (PB) of patients with diffuse large B-cell lymphoma (DLBCL). The transfer of T cell receptor (TCR) genes endows T cells with new antigen specificity. Therefore, the aim of this study is to generate diffuse large B cell lymphoma (DLBCL)-specific T cells by T cell receptor (TCR) gene transfer.<h4>Materials and methods</h4>Two different eukaryotic e ...[more]

PMID: 21223579

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Project description:IntroductionGeographic access to novel oncology therapies, and the extent to which it may vary by potential sites of care, regions, and population characteristics, is poorly understood. We examined how expanding access to chimeric antigen receptor (CAR) T cell therapy administration sites impacts patient travel distances and time.MethodsWe used geographic information system techniques to calculate shortest travel distance and time between patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) and the nearest CAR T cell therapy administration site in three scenarios: academic hospitals; academic and community multispecialty hospitals; and academic and community multispecialty hospitals plus nonacademic specialty oncology network centers. Main outcome measures were differences in travel distance and time among the scenarios and the relationship between travel time and socioeconomic status, race, rural-urban areas, and non-Hodgkin lymphoma clusters. Non-Hodgkin lymphoma incidence, socioeconomic status, and administration centers were derived from governmental/publicly available data sources.ResultsOf 3922 patients eligible for CAR T cell therapy, more than 37% had to travel more than 1 h to the nearest academic hospital. Average travel time and distance were significantly reduced by 23% and 30% (P < 0.001), respectively, when access was expanded to include community hospitals plus a broader range of oncology specialty treatment centers. Compared to academic hospitals alone, increasing access to include community hospitals decreased time and distance by 7% and 8% (P < 0.01), respectively. In addition, there would be a lower proportion of sites operating as the only care provider within 25 miles if access was expanded outside of academic hospitals only. Longer travel time was associated with lower socioeconomic status.ConclusionMany patients with DLBCL have long travel times to an academic hospital that administers CAR T cell therapy. Expanding access to care through site-of-care planning will help address regional, rural-urban, and sociodemographic equity in the geographic allocation of CAR T cell therapy.

Dataset Information

Generation of diffuse large B cell lymphoma-associated antigen-specific V?6/V?13+T cells by TCR gene transfer.

Publications

Generation of diffuse large B cell lymphoma-associated antigen-specific Vα6/Vβ13+T cells by TCR gene transfer.

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