Emerging Strategies in TCR-Engineered T Cells

Fang, Wei; Cheng, Xiao-Xia; Xue, John Z.; Xue, Shao-An

doi:10.3389/fimmu.2022.850358

Cited by 26 publications

(33 citation statements)

References 267 publications

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“…CAR-T therapy has made tremendous progress in recent years, as demonstrated by the remarkable clinical responses obtained from chimeric antigen receptor (CAR)-modified T cells (CAR-T) and T cell receptor (TCR)-engineered T cells (TCR-T). TCR-T uses specific TCRS optimized for tumor engagement and can recognize epitopes [ 43 , 44 , 45 , 46 ]. B cells in patients with autoimmune diseases can present their own antigens to autoimmune T cells to promote the release of inflammatory factors, or differentiate into plasma cells to release autoantibodies, which play an important role in the occurrence and development of autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

TCR CDR3 Sequencing as a Clue to Elucidate the Landscape of Dysimmunity in Patients with Primary Immune Thrombocytopenia

Zhan

et al. 2022

JCM

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Background: Primary immune thrombocytopenia (ITP) is an autoimmune disorder. The existence of autoreactive T cells has long been proposed in ITP. Yet the identification of autoreactive T cells has not been achieved, which is an important step to elucidate the pathogenesis of ITP. Methods: ITP patients’ peripheral blood was collected prior to the treatment and one month after initiating dexamethasone treatment per related therapeutic guideline. Serum cytokines were profiled to examine T cell subtypes imbalance using a protein chip. TCR Vβ analysis in CD8+T cells of ITP patients, and TCR CDR3 DNA sequencing of CD4+T and CD8+T cells were performed to determine the autoreactive T cells’ clones. Results: Cytokine profiling revealed imbalanced distribution of T cells subtypes, which was confirmed by CD4+T and CD8+T cells’ oligoclonal expansion of TCR Vβ analysis and TCR CDR3 DNA sequencing. VDJ segments were found to be more frequently presented in ITP patients, when compared with health controls. There was an individualized CD4+T cell or CD8+T cell CDR3 sequence in each ITP patient. Conclusions: The present study revealed that T cell clones expanded in ITP patients’ peripheral blood, and each clone had an individualized TCR CDR3 sequence. The expanded T cell clones preferred to use some specific VDJ segment. Further studies are warranted to get access to individualized treatment such as Car-T in patients with ITP.

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Section: Discussionmentioning

confidence: 99%

TCR CDR3 Sequencing as a Clue to Elucidate the Landscape of Dysimmunity in Patients with Primary Immune Thrombocytopenia

Zhan

et al. 2022

JCM

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“…T-cell receptor-engineered T-cell (TCR-T) therapy has the advantage of targeting potentially any antigen, not only those expressed on the surface of cells, such as with CAR-T-cells. Recent clinical studies on TCR-T showed meaningful results in solid tumor patients [ 191 , 192 , 193 ], with New York esophageal squamous cell carcinoma-1 (NY-ESO-1) being the most frequently targeted, with a relevant clinical response rate in metastatic melanoma and in metastatic synovial sarcoma patients [ 194 , 195 , 196 ].…”

Section: Tcr and Cancermentioning

confidence: 99%

T-Cell Receptor Repertoire Sequencing and Its Applications: Focus on Infectious Diseases and Cancer

Mazzotti

Gaimari

Bravaccini

et al. 2022

IJMS

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The immune system is a dynamic feature of each individual and a footprint of our unique internal and external exposures. Indeed, the type and level of exposure to physical and biological agents shape the development and behavior of this complex and diffuse system. Many pathological conditions depend on how our immune system responds or does not respond to a pathogen or a disease or on how the regulation of immunity is altered by the disease itself. T-cells are important players in adaptive immunity and, together with B-cells, define specificity and monitor the internal and external signals that our organism perceives through its specific receptors, TCRs and BCRs, respectively. Today, high-throughput sequencing (HTS) applied to the TCR repertoire has opened a window of opportunity to disclose T-cell repertoire development and behavior down to the clonal level. Although TCR repertoire sequencing is easily accessible today, it is important to deeply understand the available technologies for choosing the best fit for the specific experimental needs and questions. Here, we provide an updated overview of TCR repertoire sequencing strategies, providers and applications to infectious diseases and cancer to guide researchers’ choice through the multitude of available options. The possibility of extending the TCR repertoire to HLA characterization will be of pivotal importance in the near future to understand how specific HLA genes shape T-cell responses in different pathological contexts and will add a level of comprehension that was unthinkable just a few years ago.

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“…T cell infiltration into the tumor is not observed in some patients with late recurrence, and the infused TCR-T cells confront with an unfavorable immunosuppressive tumor microenvironment. In general, the application of TCR-T cells is still a challenge in many areas, including targeted immunotoxicity caused by normal tissues, low transient efficiency of TCR in engineered T cells, exhaustion and dysfunction of T cells, tumor immune escape and the lack of effective tumor-specific antigens in most patients with tumors [105] . Therefore, overcoming these challenges is key to achieving greater clinical success in the future.…”

Section: Gene and Protein In Diseasementioning

confidence: 99%

Gene-modified T cell therapy for cancer: Current challenges and potential solutions

Chen¹,

Li²,

Zhang³

et al. 2022

GPD

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Immunotherapy has achieved significant breakthroughs in patients with hematological diseases and various cancers. The adoptive transfer of T cells, especially gene-modified T cells such as chimeric antigen receptor T (CAR-T) cells and T cell receptor-engineered T (TCR-T) cells, is developing rapidly. Since 2017, eight CAR-T cell products have been approved for the treatment of hematological diseases, such as refractory or relapsed acute B lymphoblastic leukemia, specific subtypes of B cell lymphoma, and multiple myeloma. The first TCR-T cell product, Kimmtrak, was approved for the treatment of unresectable or metastatic uveal melanoma in March 2022. However, there are still many problems, including side effects, relapse, high demand for individualization, and expensive cost in hematological diseases, tumor heterogeneity, antigen escape, poor immune cell infiltration ability, immunosuppressive microenvironment, and low response in solid tumors. With the in-depth exploration of tumor immunology and the development of genetic engineering technology, many novel strategies for improving the anti-tumor effect and safety of gene-modified T cell immunotherapy have been attempted. This paper presents a systematic review of the literature on CAR-T cell and TCR-T cell therapy, focusing on applications, clinical trials, problems, and potential solutions.

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Emerging Strategies in TCR-Engineered T Cells

Cited by 26 publications

References 267 publications

TCR CDR3 Sequencing as a Clue to Elucidate the Landscape of Dysimmunity in Patients with Primary Immune Thrombocytopenia

TCR CDR3 Sequencing as a Clue to Elucidate the Landscape of Dysimmunity in Patients with Primary Immune Thrombocytopenia

T-Cell Receptor Repertoire Sequencing and Its Applications: Focus on Infectious Diseases and Cancer

Gene-modified T cell therapy for cancer: Current challenges and potential solutions

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