Curated Papers > In recent years, high-impact research in "synthetic biology" (IF ≥ 30, last 5 years)

Engineering advanced cancer therapies with synthetic biology.

Literature Information

DOI	10.1038/s41568-019-0121-0
PMID	30837696
Journal	Nature reviews. Cancer
Impact Factor	66.8
JCR Quartile	Q1
Publication Year	2019
Times Cited	42
Keywords	Synthetic Biology, Cancer Therapy, Immune Cells, Gene Circuits, Targeted Therapy
Literature Type	Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Review
ISSN	1474-175X
Pages	187-195
Issue	19(4)
Authors	Ming-Ru Wu, Barbara Jusiak, Timothy K Lu

TL;DR

This article reviews the potential of synthetic biology to enhance engineered immune-cell-based therapies for B cell malignancies by developing gene circuit therapies that target cancer cells specifically while minimizing damage to healthy cells. It highlights current advancements and challenges in the field, emphasizing the importance of these innovative approaches for improving therapeutic efficacy and addressing limitations in cancer treatment.

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Synthetic Biology · Cancer Therapy · Immune Cells · Gene Circuits · Targeted Therapy

Abstract

Engineered immune-cell-based cancer therapies have demonstrated robust efficacy in B cell malignancies, but challenges such as the lack of ideal targetable tumour antigens, tumour-mediated immunosuppression and severe toxicity still hinder their therapeutic efficacy and broad applicability. Synthetic biology can be used to overcome these challenges and create more robust, effective adaptive therapies that enable the specific targeting of cancer cells while sparing healthy cells. In this Progress article, we review recently developed gene circuit therapies for cancer using immune cells, nucleic acids and bacteria as chassis. We conclude by discussing outstanding challenges and future directions for realizing these gene circuit therapies in the clinic.

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Primary Questions Addressed

1. What specific gene circuit therapies have shown the most promise in targeting cancer cells effectively?
2. How can synthetic biology be utilized to improve the specificity of immune-cell-based therapies in various types of cancers?
3. What are the key factors contributing to tumor-mediated immunosuppression that synthetic biology aims to address?
4. In what ways can engineered bacteria serve as effective chassis for delivering cancer therapies in a clinical setting?
5. What future advancements in synthetic biology are anticipated to enhance the safety and efficacy of cancer treatments?

Key Findings

1. Research Background and Objectives

Cancer therapies utilizing engineered immune cells, particularly in treating B cell malignancies, have shown promising results. However, the widespread application of these therapies is limited by significant challenges, including the identification of suitable targetable tumor antigens, the immunosuppressive environment created by tumors, and the potential for severe toxicity in patients. The primary objective of this research is to explore how synthetic biology can be harnessed to address these challenges, thereby enabling the development of more effective and safer adaptive cancer therapies that specifically target cancer cells while minimizing harm to healthy cells.

2. Main Methods and Findings

The authors review recent advancements in gene circuit therapies that employ various biological chassis, including immune cells, nucleic acids, and bacteria. These engineered systems facilitate a more precise attack on cancer cells by utilizing sophisticated genetic circuits that can adapt to the tumor microenvironment. Notable findings highlight the potential of these gene circuits to enhance the specificity and selectivity of immune responses against cancer cells, reducing collateral damage to normal tissues. The article discusses various approaches, such as tuning immune activation, managing tumor-induced immune suppression, and improving the recognition of tumor-specific antigens.

3. Core Conclusions

The review concludes that synthetic biology holds significant promise for advancing cancer therapies through the design and implementation of gene circuit technologies. These innovations can potentially overcome the limitations faced by current immune-cell-based therapies. The authors emphasize that while there are outstanding challenges, including the need for rigorous clinical validation and the integration of these therapies into existing treatment paradigms, the advancements in gene circuit therapies represent a pivotal step toward realizing more effective and personalized cancer treatment strategies.

4. Research Significance and Impact

This research is significant as it provides a comprehensive overview of how synthetic biology can revolutionize cancer therapies, particularly in addressing the critical challenges of specificity and safety in immune-targeted treatments. The insights gained from this work could lead to breakthroughs in the design of cancer therapies that are both more effective and less toxic, ultimately improving patient outcomes. Furthermore, by integrating synthetic biology techniques, the field may move closer to personalized medicine approaches in oncology, where therapies can be tailored to the unique characteristics of individual tumors. The ongoing exploration and refinement of these gene circuit therapies could have far-reaching implications for cancer treatment protocols, potentially transforming the landscape of oncology in the coming years.

Literatures Citing This Work

1. Targeting Programmed Fusobacterium nucleatum Fap2 for Colorectal Cancer Therapy. - Kumar Ganesan;Songhe Guo;Sundaz Fayyaz;Ge Zhang;Baojun Xu - Cancers (2019)
2. LncRNAs as Chromatin Regulators in Cancer: From Molecular Function to Clinical Potential. - Rodiola Begolli;Nikos Sideris;Antonis Giakountis - Cancers (2019)
3. PiggyBac transposon system with polymeric gene carrier transfected into human T cells. - Yan Zheng;Zhan-Rong Li;Ran Yue;Yu-Long Fu;Zi-Yang Liu;Hua-Yang Feng;Jing-Guo Li;Shuang-Yin Han - American journal of translational research (2019)
4. Biosensing in Smart Engineered Probiotics. - Austin G Rottinghaus;Matthew B Amrofell;Tae Seok Moon - Biotechnology journal (2020)
5. Data-driven statistical modeling of the emergent behavior of biohybrid microrobots. - Eric J Leaman;Ali Sahari;Mahama A Traore;Brian Q Geuther;Carmen M Morrow;Bahareh Behkam - APL bioengineering (2020)
6. Synthetic Biology Speeds Up Drug Target Discovery. - Yixuan Xie;Yanfang Yang;Yu He;Xixi Wang;Peng Zhang;Haocheng Li;Shufang Liang - Frontiers in pharmacology (2020)
7. Tuning up Transcription Factors for Therapy. - Attila Becskei - Molecules (Basel, Switzerland) (2020)
8. A versatile genetic control system in mammalian cells and mice responsive to clinically licensed sodium ferulate. - Yidan Wang;Shuyong Liao;Ningzi Guan;Yuanxiao Liu;Kaili Dong;Wilfried Weber;Haifeng Ye - Science advances (2020)
9. Automated classification of bacterial cell sub-populations with convolutional neural networks. - Denis Tamiev;Paige E Furman;Nigel F Reuel - PloS one (2020)
10. A glucose meter interface for point-of-care gene circuit-based diagnostics. - Evan Amalfitano;Margot Karlikow;Masoud Norouzi;Katariina Jaenes;Seray Cicek;Fahim Masum;Peivand Sadat Mousavi;Yuxiu Guo;Laura Tang;Andrew Sydor;Duo Ma;Joel D Pearson;Daniel Trcka;Mathieu Pinette;Aruna Ambagala;Shawn Babiuk;Bradley Pickering;Jeff Wrana;Rod Bremner;Tony Mazzulli;David Sinton;John H Brumell;Alexander A Green;Keith Pardee - Nature communications (2021)

... (32 more literatures)

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