Targeting Cancer with Genetically Engineered TCR T Cells

Smith, Thomas W.; Nishimura, Michael I.

doi:10.1007/978-3-030-23765-3_4

Cited by 5 publications

(6 citation statements)

References 132 publications

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“…The TCR complex is exposed on the surface of T cells and interacts with the major histocompatibility complex (MHC), leading to activation of the cellular immune cascade. TCR transgenic T cells are genetically engineered to express receptors against specific tumor MHC and stimulate the immune response against malignant brain tumors [ 108 , 109 , 110 , 111 ]. CAR and TCR engineered T cells are expanded ex vivo and injected, cross the BBB, bind the tumor cells, and activate the antitumoral immune cascade, thus promoting apoptosis ( Figure 5 ) [ 94 , 112 , 113 , 114 , 115 ].…”

Section: Resultsmentioning

confidence: 99%

Against the Resilience of High-Grade Gliomas: The Immunotherapeutic Approach (Part I)

Lucifero

Luzzi

2021

Brain Sciences

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The resilience of high-grade gliomas (HGGs) against conventional chemotherapies is due to their heterogeneous genetic landscape, adaptive phenotypic changes, and immune escape mechanisms. Innovative immunotherapies have been developed to counteract the immunosuppressive capability of gliomas. Nevertheless, further research is needed to assess the efficacy of the immuno-based approach. The aim of this study is to review the newest immunotherapeutic approaches for glioma, focusing on the drug types, mechanisms of action, clinical pieces of evidence, and future challenges. A PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis)-based literature search was performed on PubMed/Medline and ClinicalTrials.gov databases using the keywords “active/adoptive immunotherapy,” “monoclonal antibodies,” “vaccine,” and “engineered T cell.”, combined with “malignant brain tumor”, “high-grade glioma.” Only articles written in English published in the last 10 years were selected, filtered based on best relevance. Active immunotherapies include systemic temozolomide, monoclonal antibodies, and vaccines. In several preclinical and clinical trials, adoptive immunotherapies, including T, natural killer, and natural killer T engineered cells, have been shown to be potential treatment options for relapsing gliomas. Systemic temozolomide is considered the backbone for newly diagnosed HGGs. Bevacizumab and rindopepimut are promising second-line treatments. Adoptive immunotherapies have been proven for relapsing tumors, but further evidence is needed.

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Section: Resultsmentioning

confidence: 99%

Against the Resilience of High-Grade Gliomas: The Immunotherapeutic Approach (Part I)

Lucifero

Luzzi

2021

Brain Sciences

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“…The synthetic CAR construct contains a single-chain variable fragment binding to the tumor surface antigen, transmembrane domain, and an intracellular signal transduction portion derived from CD3z and co-stimulatory molecules, such as CD28 or 4-1BB (5). The CAR detects intact antigens in a non-MHC-restricted manner and can be used in all individuals regardless of their human leukocyte antigen (HLA) type, which is an advantage of CAR over TCRengineered cells (3,10).…”

Section: Chimeric Antigen Receptor T Cellsmentioning

confidence: 99%

“…However, these challenges can be overcome by the genetic modification of T cells, reprogramming them by inserting genes that provide specificity against tumor antigens to detect and destroy cancer cells (3). To date, adoptive T-cell therapy has shown promising potential for the treatment of cancer patients.…”

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confidence: 99%

Application of Genome-Editing Technologies for Off-the-Shelf T Cell-Based Cancer Immunotherapy

Hakakzadeh

Yekehfallah

Ebrahimiyan

et al. 2021

Precis Med Clin OMICS

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: Genetically, engineered T-cell therapy is a personalized treatment that has demonstrated considerable therapeutic potential for solid tumors and hematopoietic cancers. However, endogenous T-cell receptors (TCRs) on the surface of engineered T cells hamper their application in the allogeneic settings by inducing graft-versus-host disease, where endogenous TCRs on the surface of engineered T cells respond to the recipient’s tissues. Since the cause of this allogeneic response is the TCR complex on the surface of the engineered T cells, preventing the expression of TCR components on the surface of these cells is a promising strategy to address this challenge. This review discusses the production of allogeneic chimeric antigen receptor T cells using genome-editing methods.

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“…As molecules or their preparations endowed with targeting ability, they form a relatively high concentration of drugs in the target area, so as to improve the efficacy and inhibit the toxic and side effects to normal tissues and cells. 83 Oncolytic virus also works, and oncolytic vectors are designed for improved tumour specificity, intratumoural spread, therapeutic gene delivery and especially as targeted cancer immunotherapeutics. 81 In PTT process, a photosensitizer converts the light energy to heat energy, using the temperature evolution to kill tumour cells and avoid significant side effects on normal cells because tumour cells have a lower heat tolerance than normal ones.…”

Section: The Pre S Ent S Ituati On and The Promis E Of Targ E Ting mentioning

confidence: 99%

“…82 Additionally, genetically engineered T cell with the addition of genetic material, including cytokines and cytokine receptors, enhances receptor affinity and functional avidity of the genetically engineered T cells and has got promising results in current clinical trials. 83 Oncolytic virus also works, and oncolytic vectors are designed for improved tumour specificity, intratumoural spread, therapeutic gene delivery and especially as targeted cancer immunotherapeutics. 84 The field of cancer immunotherapy has recently received a significant attention.…”

Section: The Pre S Ent S Ituati On and The Promis E Of Targ E Ting mentioning

confidence: 99%

Updates on mechanistic insights and targeting of tumour metastasis

Feng

Zhang

et al. 2020

J Cellular Molecular Medi

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Malignant tumours are one of the major diseases that seriously endanger human health. The characteristics of their invasion and metastasis are one of the main causes of death in cancer patients, and these features cannot be separated from the participation of various molecules-related cells living in the tumour microenvironment and specific structures. Tumour invasion can approximately be divided into several specific steps according to the movement of tumour cells. In each step, there are different actions in the tumour microenvironment that mediate the interactions among substances. Researchers are attempting to clarify every mechanism of the tumour dissemination. However, there is still a long way to the final determination. Here, we review these interactions in tumour invasion and metastasis at the structural, molecular and cellular levels. We also discuss the ongoing studies and the promise of targeting metastasis in tumour therapy. K E Y W O R D S metastasis, tumour invasion, tumour microenvironment | 2077 FENG Et al. How to cite this article: Feng Z, Yu Q, Zhang T, Tie W, Li J, Zhou X. Updates on mechanistic insights and targeting of tumour metastasis.

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Targeting Cancer with Genetically Engineered TCR T Cells

Cited by 5 publications

References 132 publications

Against the Resilience of High-Grade Gliomas: The Immunotherapeutic Approach (Part I)

Against the Resilience of High-Grade Gliomas: The Immunotherapeutic Approach (Part I)

Application of Genome-Editing Technologies for Off-the-Shelf T Cell-Based Cancer Immunotherapy

Updates on mechanistic insights and targeting of tumour metastasis

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