A Novel <scp>d</scp>‐Peptide Identified by Mirror‐Image Phage Display Blocks TIGIT/PVR for Cancer Immunotherapy

Zhou, Xiaoxi; Zuo, Chao; Li, Wanqiong; Shi, Weiwei; Wang, Hongfei; Chen, Shaomeng; Du, Jiangfeng; Chen, Guan-Yu; Zhai, Wenjie; Zhao, Wenshan; Wu, Yahong; Qi, Yuanming; Liu, Lei; Gao, Yanfeng

doi:10.1002/anie.202002783

Cited by 112 publications

(69 citation statements)

References 35 publications

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“…Asp‐based lactam cyclic peptide A‐183 and cyclo [Asp9,Lys13] KIIIA7‐14 lactam cyclic peptides have been successfully synthesized using an RBM strategy, wherein a 2‐hydroxy‐4‐methoxy‐ 5‐nitrobenzaldehyde group is appended to the residue immediately before Asp(OTbe), to prevent aspartimide formation. [ 32‐36 ] This RBM strategy may constitute a simple, efficient, and general method for the synthesis of Asp‐based lactam cyclic peptides, which we established to be inaccessible by direct Fmoc SPPS.…”

Section: Discussionmentioning

confidence: 99%

Use of a Removable Backbone Modification Strategy to Prevent Aspartimide Formation in the Synthesis of Asp Lactam Cyclic Peptides^†

et al. 2021

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Main observation and conclusion The synthesis of an Asp lactam derivative of A‐183, a selective inhibitor of Factor 7a with good anticoagulant and antithrombotic activity, is described. Our synthesis depends on the use of a removable backbone modification (RBM) strategy to prevent aspartimide formation, which thwarted all attempts to synthesize this target using direct solid‐phase peptide synthesis. Validation of the RBM strategy in the synthesis of a second Asp lactam derivative was also accomplished. The RBM strategy is therefore proposed as a general method for the synthesis of Asp lactam cyclic peptides.

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Section: Discussionmentioning

confidence: 99%

Use of a Removable Backbone Modification Strategy to Prevent Aspartimide Formation in the Synthesis of Asp Lactam Cyclic Peptides^†

et al. 2021

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“…[65] Sousing nanotechnology to target tumor drug delivery has excellent prospects for the enhancement of anti-tumor immunity and ICB therapy. [66] Liu and colleagues constructed a pH-responsive MSNP nanoparticle containing melanoma-specific effects (MEKI) which are encapsulated with pH-sensitive polymers and biocompatible materials. After the microparticles were injected into the body, they accumulated in the TAM, and the coated polymer promotes the internalization of the microparticles into tumor cells.…”

Section: Chemotherapymentioning

confidence: 99%

“…Commonly used nanoparticle carriers include liposomes, [61] polymer micelles, [62] polymer vesicles, [63] inorganic silica nanoparticles, [64] etc., which can achieve the controlled release of multiple drugs at tumor sites and make the combined therapy the desired pharmacokinetics and biodistribution [65] . Sousing nanotechnology to target tumor drug delivery has excellent prospects for the enhancement of anti‐tumor immunity and ICB therapy [66] …”

Section: Combination Of Nanotechnology‐based Immune Checkpoint Blockimentioning

confidence: 99%

Combined Application of Nanotechnology and Multiple Therapies with Tumor Immune Checkpoints

Sun

et al. 2020

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Tumor immunotherapy has received worldwide attention in cancer treatment owing to its apparent advantages, such as strong specificity and long curative effect. Among them, significant progress has been made on the immune checkpoint therapy in recent years. FDA approved PD‐L1/PD‐1 and CTLA‐4 immune checkpoint inhibitors have been broadly used in a variety of malignant tumors. However, because of the low response rate of immune checkpoint drugs, its clinical application has been greatly hindered. With the prominence of nanotechnology in bio‐medicine, the application of nanotechnology in immune checkpoints has also gained more and more attention. The combination of radiotherapy, chemotherapy, phototherapy, magnetic therapy and other methods in nanotechnology makes an excellent promoting effect in the treatment of immune checkpoint drugs. This article reviews the recent breakthroughs of nanotechnology in immune checkpoint blocking therapy, mainly focusing on the significant advantages of the combination of nanotechnology‐based immune checkpoint blocking therapy with other treatment methods. In addition, we also discussed the challenges in this area and pointed out some potential directions for future development.

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“…A combinational blockade of different targets with non-redundant functions may achieve better clinical benefits. A novel immune checkpoint T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (TIGIT), which always co-expresses with PD-1 on NK and T cells and symbolizes a more exhausted status, plays pivotal roles in the adaptive anti-tumor immunity by ligation with its major ligand poliovirus receptor (PVR) [ 2 , 3 ]. PVR was initially identified as the receptor for the human poliovirus, or as an adhesion-related molecule that mediates tumor invasion.…”

Section: Introductionmentioning

confidence: 99%

Repositioning Azelnidipine as a Dual Inhibitor Targeting CD47/SIRPα and TIGIT/PVR Pathways for Cancer Immuno-Therapy

et al. 2021

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Strategies boosting both innate and adaptive immunity have great application prospects in cancer immunotherapy. Antibodies dual blocking the innate checkpoint CD47 and adaptive checkpoint PD-L1 or TIGIT could achieve durable anti-tumor effects. However, a small molecule dual blockade of CD47/SIRPα and TIGIT/PVR pathways has not been investigated. Here, an elevated expression of CD47 and PVR was observed in tumor tissues and cell lines analyzed with the GEO datasets and by flow cytometry, respectively. Compounds approved by the FDA were screened with the software MOE by docking to the potential binding pockets of SIRPα and PVR identified with the corresponding structural analysis. The candidate compounds were screened by blocking and MST binding assays. Azelnidipine was found to dual block CD47/SIRPα and TIGIT/PVR pathways by co-targeting SIRPα and PVR. In vitro, azelnidipine could enhance the macrophage phagocytosis when co-cultured with tumor cells. In vivo, azelnidipine alone or combined with irradiation could significantly inhibit the growth of MC38 tumors. Azelnidipine also significantly inhibits the growth of CT26 tumors, by enhancing the infiltration and function of CD8+ T cell in tumor and systematic immune response in the tumor-draining lymph node and spleen in a CD8+ T cell dependent manner. Our research suggests that the anti-hypertensive drug azelnidipine could be repositioned for cancer immunotherapy.

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A Novel d‐Peptide Identified by Mirror‐Image Phage Display Blocks TIGIT/PVR for Cancer Immunotherapy

Cited by 112 publications

References 35 publications

Use of a Removable Backbone Modification Strategy to Prevent Aspartimide Formation in the Synthesis of Asp Lactam Cyclic Peptides^†

Use of a Removable Backbone Modification Strategy to Prevent Aspartimide Formation in the Synthesis of Asp Lactam Cyclic Peptides^†

Combined Application of Nanotechnology and Multiple Therapies with Tumor Immune Checkpoints

Repositioning Azelnidipine as a Dual Inhibitor Targeting CD47/SIRPα and TIGIT/PVR Pathways for Cancer Immuno-Therapy

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A Novel d‐Peptide Identified by Mirror‐Image Phage Display Blocks TIGIT/PVR for Cancer Immunotherapy

Cited by 112 publications

References 35 publications

Use of a Removable Backbone Modification Strategy to Prevent Aspartimide Formation in the Synthesis of Asp Lactam Cyclic Peptides†

Use of a Removable Backbone Modification Strategy to Prevent Aspartimide Formation in the Synthesis of Asp Lactam Cyclic Peptides†

Combined Application of Nanotechnology and Multiple Therapies with Tumor Immune Checkpoints

Repositioning Azelnidipine as a Dual Inhibitor Targeting CD47/SIRPα and TIGIT/PVR Pathways for Cancer Immuno-Therapy

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Use of a Removable Backbone Modification Strategy to Prevent Aspartimide Formation in the Synthesis of Asp Lactam Cyclic Peptides^†

Use of a Removable Backbone Modification Strategy to Prevent Aspartimide Formation in the Synthesis of Asp Lactam Cyclic Peptides^†