To affinity and beyond: Harnessing the T Cell receptor for cancer immunotherapy

Thaxton, Jessica E.; Li, Zihai

doi:10.4161/21645515.2014.973314

Cited by 30 publications

(21 citation statements)

References 102 publications

(103 reference statements)

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“…Affinity optimization produced improved tumor-killing ability ex vivo. However, the modification of affinity must be meticulously implemented, since improper modification can lead to cross-reactions and result in lethal adverse effects 141,254,255 .…”

Section: Binding Domainmentioning

confidence: 99%

Genetically engineered T cells for cancer immunotherapy

Zhou

et al. 2019

Sig Transduct Target Ther

185

102

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T cells in the immune system protect the human body from infection by pathogens and clear mutant cells through specific recognition by T cell receptors (TCRs). Cancer immunotherapy, by relying on this basic recognition method, boosts the antitumor efficacy of T cells by unleashing the inhibition of immune checkpoints and expands adaptive immunity by facilitating the adoptive transfer of genetically engineered T cells. T cells genetically equipped with chimeric antigen receptors (CARs) or TCRs have shown remarkable effectiveness in treating some hematological malignancies, although the efficacy of engineered T cells in treating solid tumors is far from satisfactory. In this review, we summarize the development of genetically engineered T cells, outline the most recent studies investigating genetically engineered T cells for cancer immunotherapy, and discuss strategies for improving the performance of these T cells in fighting cancers.

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Section: Binding Domainmentioning

confidence: 99%

Genetically engineered T cells for cancer immunotherapy

Zhou

et al. 2019

Sig Transduct Target Ther

185

102

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“…Two different types of receptors have been used for this purpose. One is a T cell receptor (TCR) that is engineered to detect cancer epitopes [26, 27]. The other is a chimeric antigen receptor (CAR) that is composed of a cancer antigen-specific single chain variable fragment (scFv) fused to T cell signaling domains that trigger activation and proliferation [28, 29] (Figure 1B).…”

Section: Genetic Engineering and Cellular Immunotherapy: A Potent Commentioning

confidence: 99%

Synthetic biology in cell-based cancer immunotherapy

Chakravarti

Wong

2015

Trends in Biotechnology

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The adoptive transfer of genetically engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. This form of cellular immunotherapy presents a unique opportunity to incorporate advanced systems and synthetic biology approaches to create cancer therapeutics with novel functions. Here, we first review the development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumors. In addition, we discuss the cellular engineering and genome editing of host cells (or the chassis) to improve the efficacy of cell-based cancer therapeutics, and to reduce the time and cost of manufacturing.

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“…T cells have emerged as a promising candidate for cell-based therapies, and engineering of T cells to express antigen-specific chimeric antigen receptors (CARs) have enabled programmable targeting of cancer cells [1][2][3][4] . Multiple clinical trials with CARs against B cell cancers have driven up to a 90% complete response rate in patients [5][6][7][8] , and several CAR T cell products targeting acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma have been approved for clinical use in the United States.…”

Section: Introductionmentioning

confidence: 99%

Inducible gene switches with memory in human T cells for cellular immunotherapy

Chakravarti

Caraballo

Weinberg

et al. 2018

Preprint

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Cell-based therapies that employ engineered T cells-including the expression of chimeric antigen receptors (CARs)-to target cancer cells have demonstrated promising responses in clinical trials. However, engineered T cell responses must be regulated to prevent severe side effects such as cytokine storms and off-target responses. Here we present a class of recombinase-based gene circuits that will enable inducible switching between two states of adoptive T cell therapy using an FDA-approved drug, creating a generalizable platform that can be used to control when and how strongly a gene is expressed. These circuits exhibit memory such that induced T cells will maintain any changes made even when the drug inducer is removed. This memory feature avoids prolonged drug inducer exposure, thus reducing the complexity and potential side effect associated with the drug inducer. We have utilized these circuits to control the expression of an anti-Her2-CAR, demonstrating the ability of these circuits to regulate CAR expression and T cell activity. We envision this platform can be extended to regulate other genes in T cell behavior for various adoptive T cell therapies.

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To affinity and beyond: Harnessing the T Cell receptor for cancer immunotherapy

Cited by 30 publications

References 102 publications

Genetically engineered T cells for cancer immunotherapy

Genetically engineered T cells for cancer immunotherapy

Synthetic biology in cell-based cancer immunotherapy

Inducible gene switches with memory in human T cells for cellular immunotherapy

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