Peripheral blood mononuclear cells from asymptomatic HTLV-II-infected and uninfected Gran Chaco Amerindians were analyzed using polymerase chain reaction (PCR) for expansions of T-cell receptor (TCR) V-beta gene clonotypes. Analyses were performed using primer pairs designed to identify expanded T-cell familial clonotypes based on their unique TCR beta gene rearrangements. Of the 30 HTLV-IIB-positive samples tested, five showed evidence of V-beta clonotypic T-cell expansion. Of the five expansions, two were monoclonotypic and the remaining three were oligoclonotypic. In comparison, 30 HTLV-II-negative Amerindians showed no evidence of clonotypic T-cell expansion. Amplified DNA from one of the monoclonotypic samples was subsequently cloned and sequenced and was found to have uniform variable/ diversity/joining sequences confirming its unique monoclonal T-cell expansion. This method of detecting clonal TCR beta gene rearrangements has the advantage over traditional Southern blot techniques of being more sensitive and specific even with suboptimal specimens. The prognostic significance of clonotypic T-cell expansion in a group such as the HTLV-II-infected Gran Chaco Amerindians remains to be determined.
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http://dx.doi.org/10.1097/00042560-199806010-00010 | DOI Listing |
Nat Med
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BioNTech US, Cambridge, MA, USA.
New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.
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Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
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Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
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National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, China.
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Laboratory of Molecular Immunology, Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, Russia.
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