Phage display-identified PD-L1-binding peptides reinvigorate T-cell activity and inhibit tumor progression

Gurung, Smriti; Khan, Fatima; Gunassekaran, Gowri Rangaswamy; Yoo, Jae Do; Vadevoo, Sri Murugan Poongkavithai; Permpoon, Uttapol; Kim, Sang Hyun; Kim, Ha Jeong; Kim, In San; Han, Hyeonjeong; Park, Ji Ho; Kim, Soyoun; Lee, Byungheon

doi:10.1016/j.biomaterials.2020.119984

Cited by 46 publications

(40 citation statements)

References 35 publications

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“…Programmed cell death-1 (PD-1) is a member of the B7 family that is expressed by activated T cells along with its ligand, i.e., programmed death-ligand 1 (PD-L1), to mediate immunoregulation ( 4 ). PD-L1 is another immune checkpoint cell-surface protein that is expressed by tumor cells and host cells ( 5 ). The interaction between PD-1 in T cells and PD-L1 in tumor cells leads to inhibition of the proliferation of activated T cells ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Immune Checkpoint Blockade Therapy May Be a Feasible Option for Primary Pulmonary Lymphoepithelioma-like Carcinoma

Wu¹,

Xian²,

Wang³

et al. 2021

Front. Oncol.

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Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of non-small cell lung cancer (NSCLC) for which there is currently no recognized treatment. Recently, favorable immune checkpoint blockade responses have been observed in PPLELC. This study aimed to review the effects of this regimen in patients with advanced PPLELC. PPLELC patients treated with immune checkpoint inhibitors at West China Hospital between January 2008 and December 2019 were retrospectively identified. Demographic parameters and antitumor treatment details were retrieved and reviewed. Among 128 patients diagnosed with PPLELC, 5 who received immune checkpoint inhibitors at advanced stages were included in the analysis. All of these patients were female nonsmokers with a median age of 55.6 (range 53-58) years at diagnosis. Their median PD-L1 expression was 40% (range, 30-80%). Although the patients underwent surgeries, chemotherapy and radiotherapy, all the treatments failed. Immune checkpoint inhibitors were administered palliatively, and three patients responded favorably, with the best overall response being partial remission (PR). Thus, immune checkpoint inhibitors may be a promising treatment for advanced PPLELC, and large clinical trials are warranted to obtain more evidence regarding this regimen.

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Section: Introductionmentioning

confidence: 99%

Immune Checkpoint Blockade Therapy May Be a Feasible Option for Primary Pulmonary Lymphoepithelioma-like Carcinoma

Wu¹,

Xian²,

Wang³

et al. 2021

Front. Oncol.

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“…Indeed, both PD1 and CTLA4 can downregulate the effector functions exerted by this lymphocyte subset [ 180 , 181 ]. The PDL1 expressed on tumor cells has been used to target liposomal doxorubicin with specific PDL1-binding peptides in a murine model [ 182 ]. In this system, the direct anti-tumor effect exerted by the drug was associated with the impairment of the binding between PDL1 and PD1, thus increasing the anti-tumor activity of CD8 + T cells [ 182 ].…”

Section: Np In Anti-cancer Theranostic Strategiesmentioning

confidence: 99%

“…The PDL1 expressed on tumor cells has been used to target liposomal doxorubicin with specific PDL1-binding peptides in a murine model [ 182 ]. In this system, the direct anti-tumor effect exerted by the drug was associated with the impairment of the binding between PDL1 and PD1, thus increasing the anti-tumor activity of CD8 + T cells [ 182 ]. Anti-tumor effector cells of the innate immune system, like NK and γδT cells, express low levels of immune-checkpoint molecules and display remarkable cytotoxic activity against several tumors.…”

Section: Np In Anti-cancer Theranostic Strategiesmentioning

confidence: 99%

Cancer Nanomedicine Special Issue Review Anticancer Drug Delivery with Nanoparticles: Extracellular Vesicles or Synthetic Nanobeads as Therapeutic Tools for Conventional Treatment or Immunotherapy

Zocchi

Tosetti

Benelli

et al. 2020

Cancers

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Both natural and synthetic nanoparticles have been proposed as drug carriers in cancer treatment, since they can increase drug accumulation in target tissues, optimizing the therapeutic effect. As an example, extracellular vesicles (EV), including exosomes (Exo), can become drug vehicles through endogenous or exogenous loading, amplifying the anticancer effects at the tumor site. In turn, synthetic nanoparticles (NP) can carry therapeutic molecules inside their core, improving solubility and stability, preventing degradation, and controlling their release. In this review, we summarize the recent advances in nanotechnology applied for theranostic use, distinguishing between passive and active targeting of these vehicles. In addition, examples of these models are reported: EV as transporters of conventional anticancer drugs; Exo or NP as carriers of small molecules that induce an anti-tumor immune response. Finally, we focus on two types of nanoparticles used to stimulate an anticancer immune response: Exo carried with A Disintegrin And Metalloprotease-10 inhibitors and NP loaded with aminobisphosphonates. The former would reduce the release of decoy ligands that impair tumor cell recognition, while the latter would activate the peculiar anti-tumor response exerted by γδ T cells, creating a bridge between innate and adaptive immunity.

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“…For example, small peptide, NP-12, was reported as an anti-PD-1 peptide with 29 amino acid sequence to synergize with ICD for effective ICB immunotherapy 12 . In addition, antagonist peptide of PD-L1 (CLQKTPKQC) effectively blocked the PD-1/PD-L1 interactions via high binding affinity to PD-L1 and reinvigorated the T lymphocytes, thereby inducing potent ICB immunotherapy when combined with ICD-inducing chemotherapeutic drugs 13 . However, such PD-1/PD-L1 binding peptides have shown unfavorable therapeutic efficacy owing to the extensive proteolytic cleavage and short half-lives in vivo 14 .…”

Section: Introductionmentioning

confidence: 99%

Anti-PD-L1 peptide-conjugated prodrug nanoparticles for targeted cancer immunotherapy combining PD-L1 blockade with immunogenic cell death

Moon¹,

Shim²,

Choi³

et al. 2022

Theranostics

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Rationale: Cancer immunotherapy combining immune checkpoint blockade (ICB) with chemotherapeutic drugs has provided significant clinical advances. However, such combination therapeutic regimen has suffered from severe toxicity of both drugs and low response rate of patients. In this study, we propose anti-PD-L1 peptide-conjugated prodrug nanoparticles (PD-NPs) to overcome these obstacles of current cancer immunotherapy. Methods: The functional peptide, consisted of anti-PD-L1 peptide and cathepsin B-specific cleavable peptide, is conjugated to a doxorubicin (DOX), resulting in prodrug nanoparticles of PD-NPs via intermolecular interactions. The antitumor efficacy and immune responses with minimal side effects by PD-NPs combining PD-L1 blockade and ICD are evaluated in breast tumor models. Results : The PD-NPs are taken up by PD-L1 receptor-mediated endocytosis and then induce ICD in cancer cells by DOX release. Concurrently, PD-L1 blockade by PD-NPs disrupt the immune-suppressing pathway of cancer cells, resulting in proliferation and reinvigoration of T lymphocytes. In tumor models, PD-NPs accumulate within tumor tissues via enhanced permeability and retention (EPR) effect and induce immune-responsive tumors by recruiting a large amount of immune cells. Conclusions: Collectively, targeted tumor delivery of anti-PD-L1 peptide and DOX via PD-NPs efficiently inhibit tumor progression with minimal side effects.

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Phage display-identified PD-L1-binding peptides reinvigorate T-cell activity and inhibit tumor progression

Cited by 46 publications

References 35 publications

Immune Checkpoint Blockade Therapy May Be a Feasible Option for Primary Pulmonary Lymphoepithelioma-like Carcinoma

Immune Checkpoint Blockade Therapy May Be a Feasible Option for Primary Pulmonary Lymphoepithelioma-like Carcinoma

Cancer Nanomedicine Special Issue Review Anticancer Drug Delivery with Nanoparticles: Extracellular Vesicles or Synthetic Nanobeads as Therapeutic Tools for Conventional Treatment or Immunotherapy

Anti-PD-L1 peptide-conjugated prodrug nanoparticles for targeted cancer immunotherapy combining PD-L1 blockade with immunogenic cell death

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