ArticleJournal of immunological methods2011
Development of a genetically-modified novel T-cell receptor for adoptive cell transfer against renal cell carcinoma.
Article in Journal of immunological methods, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Characterization of amino acid residues of T-cell receptors interacting with HLA-A*02-restricted antigen peptides.Annals of translational medicine · 2021Article
- Structure of MHC-Independent TCRs and Their Recognition of Native Antigen CD155.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Preclinical Evaluation of Chimeric Antigen Receptors Targeting CD70-Expressing Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Effect of the herbal formulation Jianpijiedu on the TCRVβCDR3 repertoire in rats with hepatocellular carcinoma and subjected to food restriction combined with laxative.Experimental and therapeutic medicine · 2016Article
- Co-Expansion of Cytokine-Induced Killer Cells and Vγ9Vδ2 T Cells for CAR T-Cell Therapy.PloS one · 2016Article
- Allogeneic lymphocyte-licensed DCs expand T cells with improved antitumor activity and resistance to oxidative stress and immunosuppressive factors.Molecular therapy. Methods & clinical development · 2014Article
- Distinctive features of the differentiated phenotype and infiltration of tumor-reactive lymphocytes in clear cell renal cell carcinoma.Cancer research · 2012Article
- Phenotypes and clinical significance of circulating CD4(+)CD25(+) regulatory T cells (Tregs) in patients with acute-on-chronic liver failure (ACLF).Journal of translational medicine · 2012Article
- Genetic engineering with T cell receptors.Advanced drug delivery reviews · 2012Review
- Molecular features of the complementarity determining region 3 motif of the T cell population and subsets in the blood of patients with chronic severe hepatitis B.Journal of translational medicine · 2011Article
- Molecular identification of an MHC-independent ligand recognized by a human {alpha}/{beta} T-cell receptor.Blood · 2011Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
A novel α/β T-cell clone with broad reactivity against human clear cell renal cell carcinomas (RCC) was generated from a patient with renal cancer. The T-cell receptor (TCR) from this clone recognizes soluble TNF-related apoptosis inducing ligand bound to death receptor 4, a complex found on the surface of nearly all RCC. In this study, we modified this novel TCR by introducing amino acid (AA) substitutions in its complementarity determining region 2 (CDR2) and CDR3 regions of both chains, to increase its activity. We demonstrated that tumor recognition by PBL, retrovirally-transduced with these TCRs, was decreased or unchanged by substitutions in the TCR beta chain, and in the CDR2α region. Yet some AA substitutions in the CDR3α region at positions 109 and 112 could augment tumor recognition. Specifically, substituting phenylalanine for tyrosine at AA109 (109Y-F) and alanine or lysine for serine at AA112 (112S-K or 112 S-A) augmented tumor recognition. Increased benefit was seen on combining both AA substitutions and a retrovirus encoding the modified TCR 109Y-F/112S-K conferred the best tumor recognition to transduced PBL. This modified TCR retained the recognition pattern of parental clone HC/2G-1 against RCC lines, other tumors and normal tissues. These results document that CDR3α plays an important role in the interaction of the HC/2G-1 TCR and its novel ligand. A phase I/II clinical trial, adoptively transferring autologous PBL transduced with this modified TCR has just begun in patients with metastatic RCC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.