B7-H3 as a promising target for cytotoxicity T cell in human cancer therapy

Adoptively transferred T cell-based cancer therapies have shown incredible promise in treatment of various cancers. So far therapeutic strategies using T cells have focused on manipulation of the antigen-recognition machinery itself, such as through selective expression of tumor-antigen specific T cell receptors or engineered antigen-recognition chimeric antigen receptors (CARs). While several CARs have been approved for treatment of hematopoietic malignancies, this kind of therapy has been less successful in the treatment of solid tumors, in part due to lack of suitable tumor-specific targets, the immunosuppressive tumor microenvironment, and the inability of adoptively transferred cells to maintain their therapeutic potentials. It is critical for therapeutic T cells to overcome immunosuppressive environmental triggers, mediating balanced antitumor immunity without causing unwanted inflammation or autoimmunity. To address these hurdles, chimeric receptors with distinct signaling properties are being engineered to function as allies of tumor antigen-specific receptors, modulating unique aspects of T cell function without directly binding to antigen themselves. In this review, we focus on the design and function of these chimeric non-antigen receptors, which fall into three broad categories: ‘inhibitory-to-stimulatory’ switch receptors that bind natural ligands, enhanced stimulatory receptors that interact with natural ligands, and synthetic receptor-ligand pairs. Our intent is to offer detailed descriptions that will help readers to understand the structure and function of these receptors, as well as inspire development of additional novel synthetic receptors to improve T cell-based cancer therapy.

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Drug Discovery Targeting Focal Adhesion Kinase (FAK) as a Promising Cancer Therapy

Molecules ◽

10.3390/molecules26144250 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4250

Author(s):

Xiao-Jing Pang ◽

Xiu-Juan Liu ◽

Yuan Liu ◽

Wen-Bo Liu ◽

Yin-Ru Li ◽

...

Keyword(s):

Cancer Therapy ◽

Phase I ◽

Small Molecules ◽

Anticancer Agents ◽

Biological Function ◽

Human Cancer ◽

Tumor Cell Growth ◽

Research Groups ◽

Human Cancer Cell Lines ◽

Opening Up

FAK is a nonreceptor intracellular tyrosine kinase which plays an important biological function. Many studies have found that FAK is overexpressed in many human cancer cell lines, which promotes tumor cell growth by controlling cell adhesion, migration, proliferation, and survival. Therefore, targeting FAK is considered to be a promising cancer therapy with small molecules. Many FAK inhibitors have been reported as anticancer agents with various mechanisms. Currently, six FAK inhibitors, including GSK-2256098 (Phase I), VS-6063 (Phase II), CEP-37440 (Phase I), VS-6062 (Phase I), VS-4718 (Phase I), and BI-853520 (Phase I) are undergoing clinical trials in different phases. Up to now, there have been many novel FAK inhibitors with anticancer activity reported by different research groups. In addition, FAK degraders have been successfully developed through “proteolysis targeting chimera” (PROTAC) technology, opening up a new way for FAK-targeted therapy. In this paper, the structure and biological function of FAK are reviewed, and we summarize the design, chemical types, and activity of FAK inhibitors according to the development of FAK drugs, which provided the reference for the discovery of new anticancer agents.

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The discovery of HTLV-1, the first pathogenic human retrovirus

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1521629112 ◽

2015 ◽

Vol 112 (51) ◽

pp. 15525-15529 ◽

Cited By ~ 16

Author(s):

John M. Coffin

Keyword(s):

T Cell ◽

Human Cancer ◽

Leukemia Virus ◽

Conclusive Evidence ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Culture Methods ◽

Research Knowledge ◽

Adult T Cell Leukemia ◽

Human T Cell

After the discovery of retroviral reverse transcriptase in 1970, there was a flurry of activity, sparked by the “War on Cancer,” to identify human cancer retroviruses. After many false claims resulting from various artifacts, most scientists abandoned the search, but the Gallo laboratory carried on, developing both specific assays and new cell culture methods that enabled them to report, in the accompanying 1980 PNAS paper, identification and partial characterization of human T-cell leukemia virus (HTLV; now known as HTLV-1) produced by a T-cell line from a lymphoma patient. Follow-up studies, including collaboration with the group that first identified a cluster of adult T-cell leukemia (ATL) cases in Japan, provided conclusive evidence that HTLV was the cause of this disease. HTLV-1 is now known to infect at least 4–10 million people worldwide, about 5% of whom will develop ATL. Despite intensive research, knowledge of the viral etiology has not led to improvement in treatment or outcome of ATL. However, the technology for discovery of HTLV and acknowledgment of the existence of pathogenic human retroviruses laid the technical and intellectual foundation for the discovery of the cause of AIDS soon afterward. Without this advance, our ability to diagnose and treat HIV infection most likely would have been long delayed.

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Effects of lethal irradiation and cyclosporin A treatment on the growth and tumoricidal activity of a T cell clone potentially useful in cancer therapy

Cancer Immunology Immunotherapy ◽

10.1007/bf01517345 ◽

1995 ◽

Vol 40 (3) ◽

pp. 139-151 ◽

Cited By ~ 3

Author(s):

Alessandra Cesano ◽

Sophie Visonneau ◽

Livia Cio� ◽

Steven C. Clark ◽

Daniela Santoli

Keyword(s):

T Cell ◽

Cancer Therapy ◽

Cyclosporin A ◽

Cell Clone ◽

Tumoricidal Activity ◽

T Cell Clone ◽

Lethal Irradiation

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Glyoxyl analogs of indole phytoalexins: Synthesis and anticancer activity

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc2010048 ◽

2010 ◽

Vol 75 (8) ◽

pp. 887-903 ◽

Cited By ~ 7

Author(s):

Peter Kutschy ◽

Andrej Sýkora ◽

Zuzana Čurillová ◽

Mária Repovská ◽

Martina Pilátová ◽

...

Keyword(s):

Estrogen Receptor ◽

Acute Lymphoblastic Leukemia ◽

T Cell ◽

Cell Line ◽

Human Cancer ◽

Lymphoblastic Leukemia ◽

Breast Adenocarcinoma ◽

Human Cancer Cell Lines ◽

Cell Acute Lymphoblastic Leukemia ◽

Indole Phytoalexins

Glyoxyl analogs of indole phytoalexins brassinin, 1-methoxybrassinin, brassitin, 1-methoxybrassitin and 1-methoxybrassenin B were prepared, using (1H-indol-3-yl)-, (1-methoxyindol-3-yl)- and [1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indol-3-yl]glyoxyl chlorides as starting compounds. Synthesized products were examined for their antiproliferative activity against human cancer cell lines Jurkat (T-cell acute lymphoblastic leukemia), MCF-7 (breast adenocarcinoma, estrogen receptor-positive), MDA-MB-231 (breast adenocarcinoma, estrogen receptor-negative), HeLa (cervical adenocarcinoma), CCRF-CEM cell line (T-cell acute lymphoblastic leukemia) and A-549 cell line (lung adenocarcinoma), and their activity compared with natural phytoalexins and corresponding (1H-indol-3-yl)acetic acid derivatives. The highest potency with IC50 3.3–66.1 μmol l–1 was found for glyoxyl analogs of 1-methoxybrassenin B.

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Preclinical investigations revealed possibilities for Salmonella tumor treatment. Bacteria can also be coupled to nanomaterials enabling drug-loading, photocatalytic and/or magnetic properties, using the bacteria's net negative charge

10.31219/osf.io/embqk ◽

2021 ◽

Author(s):

Moataz Dowaidar

Keyword(s):

Clinical Trials ◽

Cancer Therapy ◽

Cancer Treatment ◽

Negative Charge ◽

Human Cancer ◽

Drug Loading ◽

Tumor Therapy ◽

Preclinical Research ◽

Immunodeficient Mice ◽

Virulence Attenuation

Except in human clinical trials, preclinical tests showed the potential of Salmonella bacteria for tumor therapy. There are still various challenges to tackle before salmonella bacteria may be employed to treat human cancer. Due to its pathogenic nature, attenuation is essential to minimize the host's harmful effects of bacterial infection. Loss of anticancer efficacy from bacterial virulence attenuation can be compensated by giving therapeutic payloads to microorganisms. Bacteria can also be linked to micro-or nanomaterials with diverse properties, such as drug-loaded, photocatalytic and/or magnetic-sensing nanoparticles, using the net negative charge of the bacteria. Combining bacteria-mediated cancer treatment with other medicines that have been clinically shown to be helpful but have limits may provide surprising therapeutic results. Recently, this strategy has received attention and is underway. The use of live germs for cancer treatment has not yet been approved for human clinical trials. The non-invasive oral form of administration benefits from safety, making it more suitable for clinical cancer patients.Infection of live germs through systemic means, on the other hand, involves toxicity risk. Although Salmonella bacteria can be genetically manipulated with high tumor targeting, harm to normal tissues can not be excluded when medications with nonspecific toxicity are administered. It is preferred if the action of selected drugs may be restricted to the tumor site rather than healthy tissues, thereby boosting cancer therapy safety. In recent years, many regulatory mechanisms have been developed to manage pharmaceutical distribution through live bacterial vectors. Engineered salmonella can accumulate 1000 times greater than normal tissue density in the tumor. The QS-regulated mechanism, which initiates gene expression when bacterial density exceeds a particular threshold level, also promises Salmonella bacteria for targeted medication delivery. Nanovesicle structures of Salmonella bacteria can also be used as biocompatible nanocarriers to deliver functional medicinal chemicals in cancer therapy. Surface-modified nanovesicles preferably attach to tumor cells and are swallowed by receptor-mediated endocytosis before being destroyed to release packed drugs. The xenograft methodology, which comprises the implantation of cultivated tumor cell lines into immunodeficient mice, has often been used in preclinical research revealing favorable results about the anticancer effects of genetically engineered salmonella.

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From Drosophila segmentation to human cancer therapy

Development ◽

10.1242/dev.168898 ◽

2018 ◽

Vol 145 (21) ◽

pp. dev168898 ◽

Cited By ~ 11

Author(s):

Philip W. Ingham

Keyword(s):

Cancer Therapy ◽

Human Cancer

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