Discovery of the First Potent IDO1/IDO2 Dual Inhibitors: A Promising Strategy for Cancer Immunotherapy

Immunotherapy has recently become a promising strategy for the treatment of a wide range of cancers. However, the broad implementation of cancer immunotherapy suffers from inadequate efficacy and toxic side effects. Integrating pH-responsive nanoparticles into immunotherapy is a powerful approach to tackle these challenges because they are able to target the tumor tissues and organelles of antigen-presenting cells (APCs) which have a characteristic acidic microenvironment. The spatiotemporal control of immunotherapeutic drugs using pH-responsive nanoparticles endows cancer immunotherapy with enhanced antitumor immunity and reduced off-tumor immunity. In this review, we first discuss the cancer-immunity circle and how nanoparticles can modulate the key steps in this circle. Then, we highlight the recent advances in cancer immunotherapy with pH-responsive nanoparticles and discuss the perspective for this emerging area.

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CRISPR-Cas, a robust gene-editing technology in the era of modern cancer immunotherapy

Cancer Cell International ◽

10.1186/s12935-020-01546-8 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Seyed Mohammad Miri ◽

Elham Tafsiri ◽

William Chi Shing Cho ◽

Amir Ghaemi

Keyword(s):

T Cells ◽

Cancer Immunotherapy ◽

Gene Editing ◽

Genome Engineering ◽

Building Blocks ◽

Cell Receptor ◽

Adoptive Cell Transfer ◽

Promising Strategy ◽

Pre Treatment ◽

Cas A

Abstract Cancer immunotherapy has been emerged as a promising strategy for treatment of a broad spectrum of malignancies ranging from hematological to solid tumors. One of the principal approaches of cancer immunotherapy is transfer of natural or engineered tumor-specific T-cells into patients, a so called “adoptive cell transfer”, or ACT, process. Construction of allogeneic T-cells is dependent on the employment of a gene-editing tool to modify donor-extracted T-cells and prepare them to specifically act against tumor cells with enhanced function and durability and least side-effects. In this context, CRISPR technology can be used to produce universal T-cells, equipped with recombinant T cell receptor (TCR) or chimeric antigen receptor (CAR), through multiplex genome engineering using Cas nucleases. The robust potential of CRISPR-Cas in preparing the building blocks of ACT immunotherapy has broaden the application of such therapies and some of them have gotten FDA approvals. Here, we have collected the last investigations in the field of immuno-oncology conducted in partnership with CRISPR technology. In addition, studies that have addressed the challenges in the path of CRISPR-mediated cancer immunotherapy, as well as pre-treatment applications of CRISPR-Cas have been mentioned in detail.

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Perspectives on Oncolytic Salmonella in Cancer Immunotherapy—A Promising Strategy

Frontiers in Immunology ◽

10.3389/fimmu.2021.615930 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ding Wang ◽

Xiaodong Wei ◽

Dhan V. Kalvakolanu ◽

Baofeng Guo ◽

Ling Zhang

Keyword(s):

Cancer Immunotherapy ◽

Adverse Reactions ◽

Biological Therapy ◽

Antitumor Agent ◽

Therapeutic Benefit ◽

Immune Checkpoint Blockade ◽

Antitumor Effects ◽

Promising Strategy ◽

Car T ◽

Near Future

Since the first reported spontaneous regression of tumors in patients with streptococcus infection, cancer biological therapy was born and it evolved into today’s immunotherapy over the last century. Although the original strategy was unable to impart maximal therapeutic benefit at the beginning, it laid the foundations for the development of immune checkpoint blockade and CAR-T which are currently used for cancer treatment in the clinics. However, clinical applications have shown that current cancer immunotherapy can cause a series of adverse reactions and are captious for patients with preexisting autoimmune disorders. Salmonellae was first reported to exert antitumor effect in 1935. Until now, numerous studies have proved its potency as an antitumor agent in the near future. In this review, we summarize the currently available data on the antitumor effects of Salmonella, and discussed a possibility of integrating Salmonella into cancer immunotherapy to overcome current obstacles.

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Mining the Gut Microbiota for Microbial-Based Therapeutic Strategies in Cancer Immunotherapy

Frontiers in Oncology ◽

10.3389/fonc.2021.721249 ◽

2021 ◽

Vol 11 ◽

Author(s):

Bolei Li ◽

Tao Gong ◽

Yu Hao ◽

Xuedong Zhou ◽

Lei Cheng

Keyword(s):

Immune System ◽

Gut Microbiota ◽

Cancer Immunotherapy ◽

Critical Role ◽

Therapeutic Strategies ◽

Host Immune System ◽

The Past ◽

Promising Strategy

The past two decades witnessed a revolution in our understanding of host–microbiota interactions that led to the concept of the super-organism consisting of a eukaryotic part and a prokaryotic part. Owing to the critical role of gut microbiota in modulating the host immune system, it is not beyond all expectations that more and more evidence indicated that the shift of gut microbiota influenced responses to numerous forms of cancer immunotherapy. Therapy targeting gut microbiota is becoming a promising strategy to improve cancer immunotherapy. In this review, we discuss the role of the gut microbiota in response to cancer immunotherapy, the mechanisms that the gut microbiota influences cancer immunotherapy, and therapeutic strategies targeting gut microbiota to improve cancer immunotherapy.

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Co-delivery of anionic epitope/CpG vaccine and IDO inhibitor by self-assembled cationic liposome for combination melanoma immunotherapy

Journal of Materials Chemistry B ◽

10.1039/d1tb00256b ◽

2021 ◽

Author(s):

Qi Su ◽

Changrong Wang ◽

Huijuan Song ◽

Chuangnian Zhang ◽

Jinjian Liu ◽

...

Keyword(s):

Immune Responses ◽

Cancer Treatment ◽

Cancer Immunotherapy ◽

Cationic Liposome ◽

Antigenic Peptides ◽

Promising Strategy ◽

Self Assembled

Immunotherapy is revolutionizing cancer treatment. Vaccination of antigenic peptides has been identified as a promising strategy for cancer immunotherapy while insufficient immune responses were stimulated due to low antigenicity. Moreover,...

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Targeting SHP2 as a promising strategy for cancer immunotherapy

Pharmacological Research ◽

10.1016/j.phrs.2019.104595 ◽

2020 ◽

Vol 152 ◽

pp. 104595 ◽

Cited By ~ 13

Author(s):

Qianqian Liu ◽

Jiao Qu ◽

Mingxia Zhao ◽

Qiang Xu ◽

Yang Sun

Keyword(s):

Cancer Immunotherapy ◽

Promising Strategy

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Nanoparticles: Properties and Applications in Cancer Immunotherapy

Current Pharmaceutical Design ◽

10.2174/1381612825666190708214240 ◽

2019 ◽

Vol 25 (17) ◽

pp. 1962-1979 ◽

Cited By ~ 2

Author(s):

Alessandra Iscaro ◽

Nutter F. Howard ◽

Munitta Muthana

Keyword(s):

Cancer Immunotherapy ◽

Biomedical Applications ◽

Tumour Microenvironment ◽

Epithelial Cancer ◽

Tumour Site ◽

Hallmarks Of Cancer ◽

Stromal Compartment ◽

Complex Interactions ◽

Promising Strategy ◽

Different Types

Background:: Tumours are no longer regarded as isolated masses of aberrantly proliferating epithelial cells. Rather, their properties depend on complex interactions between epithelial cancer cells and the surrounding stromal compartment within the tumour microenvironment. In particular, leukocyte infiltration plays a role in controlling tumour development and is now considered one of the hallmarks of cancer. Thus, in the last few years, immunotherapy has become a promising strategy to fight cancer, as its goal is to reprogram or activate antitumour immunity to kill tumour cells, without damaging the normal cells and provide long-lasting results where other therapies fail. However, the immune-related adverse events due to the low specificity in tumour cell targeting, strongly limit immunotherapy efficacy. In this regard, nanomedicine offers a platform for the delivery of different immunotherapeutic agents specifically to the tumour site, thus increasing efficacy and reducing toxicity. Indeed, playing with different material types, several nanoparticles can be formulated with different shape, charge, size and surface chemical modifications making them the most promising platform for biomedical applications. Aim:: In this review, we will summarize the different types of cancer immunotherapy currently in clinical trials or already approved for cancer treatment. Then, we will focus on the most recent promising strategies to deliver immunotherapies directly to the tumour site using nanoparticles. Conclusions:: Nanomedicine seems to be a promising approach to improve the efficacy of cancer immunotherapy. However, additional investigations are needed to minimize the variables in the production processes in order to make nanoparticles suitable for clinical use.

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Targeting monoamine oxidase A-regulated TAM polarization for cancer immunotherapy

10.21203/rs.3.rs-38471/v1 ◽

2020 ◽

Author(s):

Yu-Chen Wang ◽

Xi Wang ◽

Jiaji Yu ◽

Feiyang Ma ◽

Zhe Li ◽

...

Keyword(s):

Monoamine Oxidase ◽

Cancer Immunotherapy ◽

Tumour Microenvironment ◽

Monoamine Oxidase A ◽

Promising Strategy ◽

Poor Patient ◽

Mao A ◽

The Brain ◽

Deficient Mice ◽

Poor Patient Survival

Abstract Targeting tumour-associated macrophages (TAMs) is a promising strategy to modify the immunosuppressive tumour microenvironment and improve cancer immunotherapy. Monoamine oxidase A (MAO-A) is an enzyme best known for its function in the brain; small molecule MAO inhibitors (MAOIs) are clinically used for treating neurological disorders. Here we observed MAO-A induction in mouse and human TAMs. MAO-A-deficient mice exhibited decreased TAM immunosuppressive functions corresponding with enhanced antitumour immunity. MAOI treatment induced TAM reprogramming and suppressed tumour growth in preclinical mouse syngeneic and human xenograft tumour models. Combining MAOI and anti-PD-1 treatments resulted in synergistic tumour suppression. Clinical data correlation studies associated high intratumoural MAOA expression with poor patient survival in a broad range of cancers. We further demonstrated that MAO-A promotes TAM immunosuppressive polarization via upregulating oxidative stress. Together, these data identify MAO-A as a critical regulator of TAMs and support repurposing MAOIs for TAM reprogramming to improve cancer immunotherapy.

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