Toward Synthetic Biology with Engineered T Cells: A Long Journey Just Begun

June, Carl H.

doi:10.1089/hum.2014.2533

Cited by 8 publications

(8 citation statements)

References 64 publications

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“…Designing an HIV-specific T-cell response to target the latent reservoir via gene therapy to be an effective part of an HIV cure strategy creates the opportunity to determine a priori the specificity (ie, chimeric antigen receptors [CARs]) and infectivity of activated cells (ie, CCR5 deletion) in order to ensure maximal target recognition and long-term retention. The history of cell and gene therapy to treat HIV infection has recently been reviewed [42], but it is important to emphasize that most, if not all, of the pioneering "first in human" adoptive T-cell therapy trials were performed in either HIV-infected or cancer-bearing individuals [43]. This codevelopment of cell therapy in both HIV and cancer has accelerated progress in both, and the lessons learned from each field are likely to propel each further for the foreseeable future.…”

Section: Adoptive T-cell Approachesmentioning

confidence: 99%

Cell-Mediated Immunity to Target the Persistent Human Immunodeficiency Virus Reservoir

Riley

Montaner

2017

The Journal of Infectious Diseases

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Effective clearance of virally infected cells requires the sequential activity of innate and adaptive immunity effectors. In human immunodeficiency virus (HIV) infection, naturally induced cell-mediated immune responses rarely eradicate infection. However, optimized immune responses could potentially be leveraged in HIV cure efforts if epitope escape and lack of sustained effector memory responses were to be addressed. Here we review leading HIV cure strategies that harness cell-mediated control against HIV in stably suppressed antiretroviral-treated subjects. We focus on strategies that may maximize target recognition and eradication by the sequential activation of a reconstituted immune system, together with delivery of optimal T-cell responses that can eliminate the reservoir and serve as means to maintain control of HIV spread in the absence of antiretroviral therapy (ART). As evidenced by the evolution of ART, we argue that a combination of immune-based strategies will be a superior path to cell-mediated HIV control and eradication. Available data from several human pilot trials already identify target strategies that may maximize antiviral pressure by joining innate and engineered T cell responses toward testing for sustained HIV remission and/or cure.

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Section: Adoptive T-cell Approachesmentioning

confidence: 99%

Cell-Mediated Immunity to Target the Persistent Human Immunodeficiency Virus Reservoir

Riley

Montaner

2017

The Journal of Infectious Diseases

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“…Another prime example of leveraging our knowledge in TCR signaling to treat cancer is the development of CAR T cells [108]. Early CAR designs were based on the premise that incorporation of the intracellular region of the ζ chain into a CAR is sufficient to recruit ZAP-70, evoke TCR signaling, and elicit a T cell response.…”

Section: Discussionmentioning

confidence: 99%

DCision-making in tumors governs T cell anti-tumor immunity

Alfei

2021

Oncogene

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The exploitation of T cell-based immunotherapies and immune checkpoint blockade for cancer treatment has dramatically shifted oncological treatment paradigms and broadened the horizons of cancer immunology. Dendritic cells have emerged as the critical tailors of T cell immune responses, which initiate and coordinate anti-tumor immunity. Importantly, genetic alterations in cancer cells, cytokines and chemokines produced by cancer and stromal cells, and the process of tumor microenvironmental regulation can compromise dendritic cell–T cell cross-talk, thereby disrupting anti-tumor T cell responses. This review summarizes how T cell activation is controlled by dendritic cells and how the tumor microenvironment alters dendritic cell properties in the context of the anti-tumor immune cycle. Furthermore, we will highlight therapeutic options for tailoring dendritic cell-mediated decision-making in T cells for cancer treatment.

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“…The development of cancer and HIV CAR T cell therapy has a long, intertwined, and symbiotic relationship (95), and this relationship is highlighted in Table 2. Exactly how did success with cancer CAR T cell therapy inform the design and implementation of HIV CAR T cell therapy?…”

Section: Outlook: Recent Lessons From Cancer Will Inform the Next Genmentioning

confidence: 99%

CAR Talk: How Cancer-Specific CAR T Cells Can Instruct How to Build CAR T Cells to Cure HIV

Kim

Hege²,

Riley

2019

Front. Immunol.

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Re-directing T cells via chimeric antigen receptors (CARs) was first tested in HIV-infected individuals with limited success, but these pioneering studies laid the groundwork for the clinically successful CD19 CARs that were recently FDA approved. Now there is great interest in revisiting the concept of using CAR-expressing T cells as part of a strategy to cure HIV. Many lessons have been learned on how to best engineer T cells to cure cancer, but not all of these lessons apply when developing CARs to treat and cure HIV. This mini review will focus on how early CAR T cell studies in HIV paved the way for cancer CAR T cell therapy and how progress in cancer CAR therapy has and will continue to be instructive for the development of HIV CAR T cell therapy. Additionally, the unique challenges that must be overcome to develop a successful HIV CAR T cell therapy will be highlighted.

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Toward Synthetic Biology with Engineered T Cells: A Long Journey Just Begun

Cited by 8 publications

References 64 publications

Cell-Mediated Immunity to Target the Persistent Human Immunodeficiency Virus Reservoir

Cell-Mediated Immunity to Target the Persistent Human Immunodeficiency Virus Reservoir

DCision-making in tumors governs T cell anti-tumor immunity

CAR Talk: How Cancer-Specific CAR T Cells Can Instruct How to Build CAR T Cells to Cure HIV

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