ArticleCancer immunology, immunotherapy : CII2010
Enhanced receptor expression and in vitro effector function of a murine-human hybrid MART-1-reactive T cell receptor following a rapid expansion.
Article in Cancer immunology, immunotherapy : CII, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Affinity and costimulatory architecture-associated toxicity in mesothelin-targeted TCR-mimetic CAR-T cells.Frontiers in immunology · 2026Article
- Targeting TGFβ with chimeric switch receptor and secreted trap to improve T cells anti-tumor activity.Frontiers in immunology · 2024Article
- Adoptive T-cell Immunotherapy: Perfecting Self-Defenses.Experientia supplementum (2012) · 2022Article
- Human T cells engineered with a leukemia lipid-specific TCR enables donor-unrestricted recognition of CD1c-expressing leukemia.Nature communications · 2021Article
- Review
- Review
- Massively parallel interrogation and mining of natively paired human TCRαβ repertoires.Nature biotechnology · 2020Article
- Article
- A novel Epstein-Barr virus-latent membrane protein-1-specific T-cell receptor for TCR gene therapy.British journal of cancer · 2018Article
- Stable, Nonviral Expression of Mutated Tumor Neoantigen-specific T-cell Receptors Using the Sleeping Beauty Transposon/Transposase System.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- T-cell receptor gene therapy--ready to go viral?Molecular oncology · 2015Review
- A novel murine T-cell receptor targeting NY-ESO-1.Journal of immunotherapy (Hagerstown, Md. : 1997) · 2014Article
- Genetically modified T-cell therapy for osteosarcoma.Advances in experimental medicine and biology · 2014Review
- Genetically modified T cells to target glioblastoma.Frontiers in oncology · 2013Review
- Gene expression profiling using nanostring digital RNA counting to identify potential target antigens for melanoma immunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- Human ovarian tumor ascites fluids rapidly and reversibly inhibit T cell receptor-induced NF-κB and NFAT signaling in tumor-associated T cells.Cancer immunity · 2013Article
- A Promising Vector for TCR Gene Therapy: Differential Effect of siRNA, 2A Peptide, and Disulfide Bond on the Introduced TCR Expression.Molecular therapy. Nucleic acids · 2012Article
- The past, present, and future of adoptive T cell therapy.Immune network · 2012Article
- Single-chain VαVβ T-cell receptors function without mispairing with endogenous TCR chains.Gene therapy · 2012Article
- A simple and effective method to generate lentiviral vectors for ex vivo gene delivery to mature human peripheral blood lymphocytes.Human gene therapy methods · 2012Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Peripheral blood lymphocytes (PBL) genetically modified to express T cell receptors (TCR) specific to known melanoma antigens, such as melanoma antigen recognized by T cells-1 (MART-1), and gp100 can elicit objective tumor regression when administered to patients with metastatic melanoma. It has also been demonstrated that modifications within the constant regions of a fully human TCR can enhance surface expression and stability without altering antigen specificity. In this study, we evaluated the substitution of murine constant regions for their human counterpart within the DMF5 MART-1-specific TCR. Unlike previous studies, all modified TCRs were inserted into retroviral vectors and analyzed for expression and function following a clinical transduction protocol. PBL were transduced with retroviral supernatant generated from stable packaging lines encoding melanoma-specific TCRs. This protocol resulted in high levels of antigen-specific T cells without the need for additional peptide stimulation and selection. Both the human and murinized TCR efficiently transduced PBL; however, the murinized TCR exhibited significantly higher tetramer binding, mean fluorescence intensity, as well as, increased in vitro effector function following our clinical transduction and expansion protocol. Additional TCR modifications including insertion of a second disulfide bond or the linker modifications evaluated herein did not significantly enhance TCR expression or subsequent in vitro effector function. We conclude that the substitution of a human constant region with a murine constant region was sufficient to increase receptor expression and tetramer binding as well as antitumor activity of the DMF5 TCR and could be a tool to augment other antigen-specific TCR.
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Registered trials
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.