Engineering Principles for Synthetic Biology Circuits in Cancer Immunotherapy

Shih, Ryan; Chen, Yvonne Y.

doi:10.1158/2326-6066.cir-21-0769

Cited by 7 publications

(6 citation statements)

References 42 publications

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“…To achieve safe, potent, and durable therapeutic benefit, cellbased therapies must meet a number of performance criteria: (i) precise targeting of tumor cells and simultaneous avoidance of essential healthy tissue, (ii) complete coverage of the tumor population based on antigen recognition, and (iii) robust expansion and functional persistence of the effector cell population to eradicate existing tumor burden and provide long-term surveillance against tumor relapse. The first two objectives are most typically achieved through careful antigen selection and receptor engineering, a topic that has been extensively covered in several reviews [71,72]. Here, we discuss strategies aimed at promoting the expansion and functional persistence of engineered cells post-infusion.…”

Section: Genetic Modifications To Enhance T-cell Potencymentioning

confidence: 99%

Successes and challenges in clinical gene therapy

Kohn,

Chen,

Spencer

2023

Gene Ther

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Despite the ups and downs in the field over three decades, the science of gene therapy has continued to advance and provide enduring treatments for increasing number of diseases. There are active clinical trials approaching a variety of inherited and acquired disorders of different organ systems. Approaches include ex vivo modification of hematologic stem cells (HSC), T lymphocytes and other immune cells, as well as in vivo delivery of genes or gene editing reagents to the relevant target cells by either local or systemic administration. In this article, we highlight success and ongoing challenges in three areas of high activity in gene therapy: inherited blood cell diseases by targeting hematopoietic stem cells, malignant disorders using immune effector cells genetically modified with chimeric antigen receptors, and ophthalmologic, neurologic, and coagulation disorders using in vivo administration of adeno-associated virus (AAV) vectors. In recent years, there have been true cures for many of these diseases, with sustained clinical benefit that exceed those from other medical approaches. Each of these treatments faces ongoing challenges, namely their high one-time costs and the complexity of manufacturing the therapeutic agents, which are biological viruses and cell products, at pharmacologic standards of quality and consistency. New models of reimbursement are needed to make these innovative treatments widely available to patients in need.

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Section: Genetic Modifications To Enhance T-cell Potencymentioning

confidence: 99%

Successes and challenges in clinical gene therapy

Kohn,

Chen,

Spencer

2023

Gene Ther

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“…Despite their long history, the use of bacteria as therapeutics has yet to be fully explored, and they have not been as widely adopted as traditional drug therapies. This is partly due to the difficulty in engineering bacteria, but with advances in synthetic biology, this challenge can be overcome 4,6,9,16,17 . The ability to precisely manipulate and control the genetic information of bacteria owing to synthetic biology has opened novel avenues to create tailored anti-cancer therapeutic strategies with improved specificity and efficacy 18 .…”

Section: Introductionmentioning

confidence: 99%

A Bacterial Living Therapeutics with Engineered Protein Secretion Circuits To Eliminate Breast Cancer Cells

Shahid

Ahan

Ostaku

et al. 2023

Preprint

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Cancer therapy can be limited by potential side effects, and bacteria-based living cancer therapeutics have gained scientific interest in recent years. However, the full potential of bacteria as therapeutics has yet to be explored due to engineering challenges. n this study, we present a bacterial device designed to specifically target and eliminate breast cancer cells. We have engineered Escherichia coli (E. coli) to secrete a Shiga toxin, HlyE, which is a pore-forming protein that binds to HER2 receptors on breast cancer cells. This binding is facilitated by a nanobody expressed on the bacteria's surface via the Ag43 autotransporter protein system. Our findings demonstrate that the nanobody efficiently binds to HER2+ cells in vitro, and we have utilized the YebF secretion system to secrete HlyE and kill the target cancer cells. Overall, our results highlight the potential of our engineered bacteria as an innovative strategy for breast cancer treatment.

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“…35,36 Although genetic engineering technologies are developed to endow cells with new functions, they are timeconsuming, costly, and have a poor success rate, leading to a long production cycle. [37][38][39][40][41][42] Therefore, new strategies are needed to overcome the challenges of DDSs. As an emerging chemical modification technique, bioorthogonal chemistry has shown enormous potential in developing DDSs.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in developing active targeting and multi-functional drug delivery systems via bioorthogonal chemistry

Xiao

Liu

et al. 2022

Sig Transduct Target Ther

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Bioorthogonal chemistry reactions occur in physiological conditions without interfering with normal physiological processes. Through metabolic engineering, bioorthogonal groups can be tagged onto cell membranes, which selectively attach to cargos with paired groups via bioorthogonal reactions. Due to its simplicity, high efficiency, and specificity, bioorthogonal chemistry has demonstrated great application potential in drug delivery. On the one hand, bioorthogonal reactions improve therapeutic agent delivery to target sites, overcoming off-target distribution. On the other hand, nanoparticles and biomolecules can be linked to cell membranes by bioorthogonal reactions, providing approaches to developing multi-functional drug delivery systems (DDSs). In this review, we first describe the principle of labeling cells or pathogenic microorganisms with bioorthogonal groups. We then highlight recent breakthroughs in developing active targeting DDSs to tumors, immune systems, or bacteria by bioorthogonal chemistry, as well as applications of bioorthogonal chemistry in developing functional bio-inspired DDSs (biomimetic DDSs, cell-based DDSs, bacteria-based and phage-based DDSs) and hydrogels. Finally, we discuss the difficulties and prospective direction of bioorthogonal chemistry in drug delivery. We expect this review will help us understand the latest advances in the development of active targeting and multi-functional DDSs using bioorthogonal chemistry and inspire innovative applications of bioorthogonal chemistry in developing smart DDSs for disease treatment.

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Engineering Principles for Synthetic Biology Circuits in Cancer Immunotherapy

Cited by 7 publications

References 42 publications

Successes and challenges in clinical gene therapy

Successes and challenges in clinical gene therapy

A Bacterial Living Therapeutics with Engineered Protein Secretion Circuits To Eliminate Breast Cancer Cells

Recent advances in developing active targeting and multi-functional drug delivery systems via bioorthogonal chemistry

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