Treating cancer with infection: a review on bacterial cancer therapy

There is an increasing need for new cancer therapies. The antitumour effect of bacterial infection has been well observed and practiced throughout history. Bacteria are well‐suited to serve as anticancer agents due to their intrinsic mobility, cell toxicity, immunogenicity, and preferential accumulation within the anoxic tumour environment. Furthermore, advances in biotechnology and molecular techniques have made it easier than ever to engineer bacteria as both therapeutic agents themselves and as therapeutic vectors. Here, we review bacteriolytic therapy and immunotherapy strategies, and examine the development of bacteria as vehicles for cell‐ and tissue‐targeted delivery of genetic cancer therapeutics.     

Addressing cancer immunotherapy research in Iran: adoptive cell therapy on the horizon

Recent advances in immunotherapeutic modalities have profoundly changed the prospect of cancer treatment. These modalities mainly focus on modulating the immune response toward tumor cells by using monoclonal antibodies, cancer vaccines, adoptive cell transfer or combination of these methods. In the last few years, Iranian scientists have conducted several projects in these arenas. Here, we provide an overview of these studies and analyze the quality and trend of publications in each sub-specialty of the field. In addition, the contribution of different universities and scientific institutes is assessed. This study may benefit scientific community and policymakers to plan future cancer immunotherapies in Iran and other countries.     

Modular design of synthetic receptors for programmed gene regulation in cell therapies

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Drugging the addict: non‐oncogene addiction as a target for cancer therapy

Historically, cancers have been treated with chemotherapeutics aimed to have profound effects on tumor cells with only limited effects on normal tissue. This approach was followed by the development of small‐molecule inhibitors that can target oncogenic pathways critical for the survival of tumor cells. The clinical targeting of these so‐called oncogene addictions, however, is in many instances hampered by the outgrowth of resistant clones. More recently, the proper functioning of non‐mutated genes has been shown to enhance the survival of many cancers, a phenomenon called non‐oncogene addiction. In the current review, we will focus on the distinct non‐oncogenic addictions found in cancer cells, including synthetic lethal interactions, the underlying stress phenotypes, and arising therapeutic opportunities.     

Syn Wiki: Functional annotation of the first artificial organism Mycoplasma mycoides JCVI‐syn3A

The new field of synthetic biology aims at the creation of artificially designed organisms. A major breakthrough in the field was the generation of the artificial synthetic organism Mycoplasma mycoides JCVI‐syn3A. This bacterium possesses only 452 protein‐coding genes, the smallest number for any organism that is viable independent of a host cell. However, about one third of the proteins have no known function indicating major gaps in our understanding of simple living cells. To facilitate the investigation of the components of this minimal bacterium, we have generated the database SynWiki (http://synwiki.uni-goettingen.de/). SynWiki is based on a relational database and gives access to published information about the genes and proteins of M. mycoides JCVI‐syn3A. To gain a better understanding of the functions of the genes and proteins of the artificial bacteria, protein–protein interactions that may provide clues for the protein functions are included in an interactive manner. SynWiki is an important tool for the synthetic biology community that will support the comprehensive understanding of a minimal cell as well as the functional annotation of so far uncharacterized proteins.     

The importance and future of biochemical engineering

Today's Biochemical Engineer may contribute to advances in a wide range of technical areas. The recent Biochemical and Molecular Engineering XXI conference focused on “The Next Generation of Biochemical and Molecular Engineering: The role of emerging technologies in tomorrow's products and processes”. On the basis of topical discussions at this conference, this perspective synthesizes one vision on where investment in research areas is needed for biotechnology to continue contributing to some of the world's grand challenges.     

Microenvironmental ammonia enhances T cell exhaustion in colorectal cancer

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Short-circuiting the cell cycle for cancer therapy

Comment on: Carrassa L, et al. Cell Cycle 2012; 2507-17.     

Short-circuiting the cell cycle for cancer therapy

Comment on: Carrassa L, et al. Cell Cycle 2012; 2507-17.     

Recent advances in mRNA-based vaccine for cancer therapy; bench to bedside

The messenger RNA (mRNA) vaccines have progressed from a theoretical concept to a clinical reality over the last few decades. Compared to conventional vaccination methods, these vaccines have a number of benefits, such as substantial potency, rapid growth, inexpensive production, and safe administration. Nevertheless, their usefulness was restricted up to now due to worries about the erratic and ineffective circulation of mRNA in vivo. Thankfully, these worries have largely been allayed by recent technological developments, which have led to the creation of multiple mRNA vaccination platforms for cancer and viral infections. The mRNA vaccines have been demonstrated as a powerful alternative to traditional conventional vaccines because of their high potency, safety and efficacy, capacity for rapid clinical development, and potential for rapid, low-cost manufacturing. The paper will examine the present status of mRNA vaccine technology and suggest future paths for the advancement and application of this exciting vaccine platform as a common therapeutic choice.     

Engineering a customizable antibacterial T6SS‐based platform in Vibrio natriegens

Bacterial pathogens are a major risk to human, animal, and plant health. To counteract the spread of antibiotic resistance, alternative antibacterial strategies are urgently needed. Here, we construct a proof‐of‐concept customizable, modular, and inducible antibacterial toxin delivery platform. By engineering a type VI secretion system (T6SS) that is controlled by an externally induced on/off switch, we transform the safe bacterium, Vibrio natriegens, into an effective antibacterial weapon. Furthermore, we demonstrate that the delivered effector repertoire, and thus the toxicity range of this platform, can be easily manipulated and tested. We believe that this platform can serve as a foundation for novel antibacterial bio‐treatments, as well as a unique tool to study antibacterial toxins.     

Dendritic cell/cytokine-induced killer cell-based immunotherapy in lung cancer: What we know and future landscape

Multiple modalities for lung cancer therapy have emerged in the past decade, whereas their clinical applications and survival-beneficiary is little known. Vaccination with dendritic cells (DCs) or DCs/cytokine-induced killer (CIK) cells has shown limited success in the treatment of patients with advanced non-small-cell lung cancer. To evaluate and overcome these limitations in further studies, in the present review, we sum up recent progress about DCs or DCs/CIKs-based approaches for preclinical and clinical trials in patients with lung cancer and discuss some of the limited therapeutic success. Moreover, this review highlights the need to focus future studies on the development of new approaches for successful immunotherapy in patients with lung cancer.     

Road to the future of systems biotechnology: CRISPR-Cas-mediated metabolic engineering for recombinant protein production

The rising potential for CRISPR–Cas-mediated genome editing has revolutionized our strategies in basic and practical bioengineering research. It provides a predictable and precise method for genome modification in a robust and reproducible fashion. Emergence of systems biotechnology and synthetic biology approaches coupled with CRISPR–Cas technology could change the future of cell factories to possess some new features which have not been found naturally. We have discussed the possibility and versatile potentials of CRISPR–Cas technology for metabolic engineering of a recombinant host for heterologous protein production. We describe the mechanisms involved in this metabolic engineering approach and present the diverse features of its application in biotechnology and protein production.     

Current approaches in dendritic cell generation and future implications for cancer immunotherapy

The discovery of tumor-associated antigens, which are either selectively or preferentially expressed by tumors, together with an improved insight in dendritic cell biology illustrating their key function in the immune system, have provided a rationale to initiate dendritic cell-based cancer immunotherapy trials. Nevertheless, dendritic cell vaccination is in an early stage, as methods for preparing tumor antigen presenting dendritic cells and improving their immunostimulatory function are continuously being optimized. In addition, recent improvements in immunomonitoring have emphasized the need for careful design of this part of the trials. Still, valuable proofs-of-principle have been obtained, which favor the use of dendritic cells in subsequent, more standardized clinical trials. Here, we review the recent developments in clinical DC generation, antigen loading methods and immunomonitoring approaches for DC-based trials.     

Immunotherapy in colorectal cancer: current achievements and future perspective

Following dramatic success in many types of advanced solid tumors, interest in immunotherapy for the treatment of colorectal cancer (CRC) is increasingly growing. Given the compelling long-term durable remission, two programmed cell death 1 (PD-1)-blocking antibodies, pembrolizumab and nivolumab (with or without Ipilimumab), have been approved for the treatment of patients with metastatic colorectal cancer (mCRC) that is mismatch-repair-deficient and microsatellite instability-high (dMMR-MSI-H). Practice-changing results of several randomized controlled trials to move immunotherapy into the first-line treatment for MSI-H metastasis cancer and earlier stage were reported successively in the past 2 years. Besides, new intriguing advances to expand the efficacy of immunotherapy to mCRC that is mismatch-repair-proficient and low microsatellite instability (pMMR-MSI-L) demonstrated the potential benefits for the vast majority of mCRC cases. Great attention is also paid to the advances in cancer vaccines and adoptive cell therapy (ACT). In this review, we summarize the above progresses, and also highlight the current predictive biomarkers of responsiveness in immunotherapy with broad clinical utility.     

Recent advances in engineering of microbial cell factories for intelligent pH regulation and tolerance

pH regulation is a serious concern in the industrial fermentation process as pH adjustment heavily utilizes acid/base and pollutes the environment. Under pH-stress conditions, microbial growth and production of valuable target products may be severely affected. Furthermore, some strains generating acidic or alkaline products require self pH regulation and increased tolerance against pH-stress. For pH control, synthetic biology has provided advanced engineering approaches to construct robust and more intelligent microbial strains, exhibiting tolerance to pH-stress to cope with limitations of pH regulation. This study reviewed the current progress of advanced strain evolution strategies to engineer pH-stress tolerant strains via synthetic biology. In addition, a large number of pH-responsive elements, including promoters, riboswitches, and some proteins have been investigated and applied for construction of pH-responsive genetic circuits and intelligent pH-responsive microbial strains.     

Bacterial l-asparaginases for cancer therapy: Current knowledge and future perspectives

l -Asparaginases hydrolyzing plasma l -asparagine and l -glutamine has attracted tremendous attention in recent years owing to remarkable anticancer properties. This enzyme is efficiently used for acute lymphoblastic leukemia (ALL) and lymphosarcoma and emerged against ALL in children, neoplasia, and some other malignancies. Cancer cells reduce the expression of l -asparaginase leading to their elimination. The l -asparaginase anticancerous application approach has made incredible breakthrough in the field of modern oncology through depletion of plasma l -asparagine to inhibit the cancer cells growth; particularly among children. High level of l -asparaginase enzyme production by Escherichia coli, Erwinia species, Streptomyces, and Bacillus subtilis species is highly desirable as bacterial alternative enzyme sources for anticancer therapy. Thermal or harsh conditions stability of those from the two latter bacterial species is considerable. Some enzymes from marine bacteria have conferred stability in adverse conditions being more advantageous in cancer therapy. Several side effects exerted by l -asparaginases such as hypersensitivity should be hindered or decreased through alternative therapies or use of immune-suppressor drugs. The l -asparaginase from Erwinia species has displayed remarkable traits in children with this regard. Noticeably, Erwinia chrysanthemi l -asparaginase exhibited negligible glutaminase activity representing a promising efficiency mitigating related side effects. Application of software such as RSM would optimize conditions for higher levels of enzyme production. Additionally, genetic recombination of the encoding gene would indisputably help improving enzyme traits. Furthermore, the possibility of anticancer combination therapy using two or more l -asparaginases from various sources is plausible in future studies to achieve better therapeutic outcomes with lower side effects.