Small molecule-based immunomodulators for cancer therapy

Wu, Yinrong; Yang, Zhilu; Cheng, Kui; Bi, Huichang; Chen, Jianjun

doi:10.1016/j.apsb.2022.11.007

Cited by 42 publications

(25 citation statements)

References 167 publications

(169 reference statements)

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“…In the small molecule arena, the targeting of tetraspanin lags far behind the design and development of monoclonal antibodies. The situation is not unique, even common in the category of immune checkpoint inhibitors for example, with many mAbs approved (13 targeting the PD-1/PD-L1 checkpoint) but not a single small molecule in advanced clinical development against the same checkpoint, despite the many categories of anti-PD-L1 small molecules discovered [ 172 , 173 , 174 ]. However, in the tetraspanin field, the gap is huge because there is a major deficit of tetraspanin-binding small molecules.…”

Section: Discussionmentioning

confidence: 99%

Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases

Bailly

Thuru

2023

Cancers

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Tetraspanin CD81 plays major roles in cell-cell interactions and the regulation of cellular trafficking. This cholesterol-embarking transmembrane protein is a co-receptor for several viruses, including HCV, HIV-1 and Chikungunya virus, which exploits the large extracellular loop EC2 for cell entry. CD81 is also an anticancer target implicated in cancer cell proliferation and mobility, and in tumor metastasis. CD81 signaling contributes to the development of solid tumors (notably colorectal, liver and gastric cancers) and has been implicated in the aggressivity of B-cell lymphomas. A variety of protein partners can interact with CD81, either to regulate attachment and uptake of viruses (HCV E2, claudin-1, IFIM1) or to contribute to tumor growth and dissemination (CD19, CD44, EWI-2). CD81-protein interactions can be modulated with molecules targeting the extracellular domain of CD81, investigated as antiviral and/or anticancer agents. Several monoclonal antibodies anti-CD81 have been developed, notably mAb 5A6 active against invasion and metastasis of triple-negative breast cancer cells. CD81-EC2 can also be targeted with natural products (trachelogenin and harzianoic acids A-B) and synthetic compounds (such as benzothiazole-quinoline derivatives). They are weak CD81 binders but offer templates for the design of new compounds targeting the open EC2 loop. There is no anti-CD81 compound in clinical development at present, but this structurally well-characterized tetraspanin warrants more substantial considerations as a drug target.

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Section: Discussionmentioning

confidence: 99%

Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases

Bailly

Thuru

2023

Cancers

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“…As neither PD-L1 nor PD-1 has a deep binding pocket, their interaction occurs at a hydrophobic, flat, and extended (~1.700 A) interface. Another challenge for small molecule immuno-oncology drugs is that many immunotherapeutic targets and pathways are interconnected, meaning that modulation of one target may affect other immune signaling pathways 61 . As such, a growing number of studies are focusing on addressing these challenges.…”

Section: Clinical Applications Of Pd-l1mentioning

confidence: 99%

Recent Advancement of PD-L1 Detection Technologies and Clinical Applications in the Era of Precision Cancer Therapy

Zhang¹,

Wu²,

Zhao³

et al. 2023

J. Cancer

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Programmed death-1 is a protein found on the surface of immune cells that can interact with its ligand, programmed death-ligand 1 (PD-L1), which is expressed on the plasma membrane, the surface of secreted cellular exosomes, in cell nuclei, or as a circulating soluble protein. This interaction can lead to immune escape in cancer patients. In clinical settings, PD-L1 plays an important role in tumor disease diagnosis, determining therapeutic effectiveness, and predicting patient prognosis. PD-L1 inhibitors are also essential components of tumor immunotherapy. Thus, the detection of PD-L1 levels is crucial, especially in the era of precision cancer therapy. In recent years, innovations have been made in traditional immunoassay methods and the development of new immunoassays for PD-L1 detection. This review aims to summarize recent research progress in tumor PD-L1 detection technology and highlight the clinical applications of PD-L1.

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“…8 Up to now, the research of small-molecule immune drugs has made positive progress, including toll-like receptors (TLRs) and stimulator of interferon genes (STING). 9,10 TLRs are a class of pattern recognition receptors, which play a critical role in the innate immune system. 11−13 At present, TLR agonists entering clinical studies for tumor immunotherapy are mainly TLR7/8 and TLR4 agonists.…”

Section: Introductionmentioning

confidence: 99%

“…At the same time, small-molecule drugs have a shorter half-life and reduce the accumulation of drugs in the systemic circulation, resulting in lower systemic toxicity and side effects . Up to now, the research of small-molecule immune drugs has made positive progress, including toll-like receptors (TLRs) and stimulator of interferon genes (STING). , TLRs are a class of pattern recognition receptors, which play a critical role in the innate immune system. − At present, TLR agonists entering clinical studies for tumor immunotherapy are mainly TLR7/8 and TLR4 agonists . When TLR7/8 is activated, the downstream connective protein myeloid differentiation factor 88 (MyD88) is rapidly recruited to activate the nuclear factor kappa-B (NF-κB) pathway, trigger the release of tumor necrosis factor (TNF)-α and other cytokines, and activate the innate immune system .…”

Section: Introductionmentioning

confidence: 99%

Cancer Cell Membrane-Coated Nanoparticle Co-loaded with Photosensitizer and Toll-like Receptor 7 Agonist for the Enhancement of Combined Tumor Immunotherapy

Chen,

Zhi,

et al. 2023

ACS Nano

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Small molecule-based immunomodulators for cancer therapy

Cited by 42 publications

References 167 publications

Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases

Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases

Recent Advancement of PD-L1 Detection Technologies and Clinical Applications in the Era of Precision Cancer Therapy

Cancer Cell Membrane-Coated Nanoparticle Co-loaded with Photosensitizer and Toll-like Receptor 7 Agonist for the Enhancement of Combined Tumor Immunotherapy

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