Programmed Cell Death Protein 1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) Immunotherapy: A Promising Breakthrough in Cancer Therapeutics

Cureus, Год журнала: 2023, Номер unknown

Опубликована: Сен. 2, 2023

The advent of immune checkpoint inhibitors has revolutionized cancer therapy by leveraging the body's system to combat malignancies effectively. Among these groundbreaking agents, programmed cell death protein 1 (PD-1) and ligand (PD-L1) have emerged as pivotal therapeutic approaches. PD-L1, a key expressed on surface various cells, including plays central role in regulation interacting with receptor T-cells leading suppression. substantial increase PD-L1 expression surfaces driven exploration PD-1/PD-L1 potential immunotherapeutic agents. These are monoclonal antibodies designed impede PD-1 interaction disrupt immunosuppressive signal, thereby reinvigorating anti-tumor response mediated activated T-cells. Clinical trials investigating demonstrated remarkable efficacy treatment diverse advanced or metastatic cancers, leukemia, non-small lung (NSCLC), hepatocellular, melanoma, gastric, colorectal, breast among others. Regulatory approvals been granted for both monotherapy combination other treatments, encompassing chemotherapy additional inhibitors. While exhibited significant success, they not devoid challenges. emergence intrinsic acquired resistance, well immune-related adverse events, warrants thorough investigation management. Consequently, researchers embarked augment surmount resistance mechanisms.

Язык: Английский

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The emerging and challenging role of PD-L1 in patients with gynecological cancers: An updating review with clinico-pathological considerations

Gynecologic Oncology, Год журнала: 2024, Номер 184, С. 57 - 66

Опубликована: Янв. 30, 2024

Over recent years, there has been significant progress in the development of immunotherapeutic molecules designed to block PD-1/PD-L1 axis. These have demonstrated their ability enhance immune response by prompting T cells identify and suppress neoplastic cells. PD-L1 is a type 1 transmembrane protein ligand expressed on lymphocytes, B antigen-presenting considered key inhibitory checkpoint involved cancer regulation. immunohistochemical expression gynecological malignancies extremely variable based tumor stage molecular subtypes. As result, class monoclonal antibodies targeting PD-1 receptor PD-L1, known as inhibitors, found successful application clinical settings. In practice, standard method for identifying suitable candidates inhibitor therapy involves assessment tissues. The most commonly used assays trials are SP142, 28-8, 22C3, SP263, each which rigorously validated specific platforms. Gynecologic cancers encompass wide spectrum originating from ovaries, uterus, cervix, vulva. neoplasms shown immunotherapy appears be influenced genetic profiles, including factors such mismatch repair status, mutational burden, expression. present paper, an extensive review various gynecologic types discussed, providing guide pathological reporting.

Язык: Английский

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Receptor-Targeted Nanomedicine for Cancer Therapy

Receptors, Год журнала: 2024, Номер 3(3), С. 323 - 361

Опубликована: Июль 3, 2024

Receptor-targeted drug delivery has been extensively explored for active targeting of therapeutic moiety in cancer treatment. In this review, we discuss the receptors that are overexpressed on tumor cells and have potential to be targeted by nanocarrier systems We also highlight different types ligands researchers explored. Our discussion covers various modalities, including small molecules, aptamers, peptides, antibodies, cell-based strategies, focuses clinical developments. Additionally, article highlights challenges arise during translation nanocarrier-based strategies. It provides future directions improving research area clinically translatable cancer-targeted therapy improve treatment efficacy while minimizing toxicity.

Язык: Английский

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Profiling phagosome proteins identifies PD-L1 as a fungal-binding receptor

Nature, Год журнала: 2024, Номер 630(8017), С. 736 - 743

Опубликована: Июнь 5, 2024

Язык: Английский

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The Matrix Stiffness Coordinates the Cell Proliferation and PD-L1 Expression via YAP in Lung Adenocarcinoma

Cancers, Год журнала: 2024, Номер 16(3), С. 598 - 598

Опубликована: Янв. 31, 2024

The extracellular matrix (ECM) exerts physiological activity, facilitates cell-to-cell communication, promotes cell proliferation and metastasis, provides mechanical support for tumor cells. development of solid tumors is often associated with increased stiffness. A stiff ECM mechanotransduction, the predominant transcription factors implicated in this phenomenon are YAP/TAZ, β-catenin, NF-κB. In study, we aimed to investigate whether YAP a critical mediator linking stiffness PD-L1 lung adenocarcinoma. We confirmed that YAP, PD-L1, Ki-67, marker proliferation, increase as increases vitro using adenocarcinoma lines PC9 HCC827 knockdown decreased expression conversely, overexpression K-67 stiff-matrix environment (20.0 kPa). Additionally, cancer cells were cultured 3D environment, which more physiologically relevant setting, compared results obtained from 2D culture. Similar findings culture, it was influenced culture experiment. Our suggest controls via activation, ultimately contributing proliferation.

Язык: Английский

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Open-label, phase Ia study of STING agonist BI 1703880 plus ezabenlimab for patients with advanced solid tumors

Future Oncology, Год журнала: 2025, Номер 21(2), С. 195 - 200

Опубликована: Янв. 14, 2025

BI 1703880, a novel STimulator of INterferon Genes (STING) agonist, has demonstrated preclinical antitumor activity. As STING activation can upregulate programmed death ligand 1 and human leukocyte antigen in tumor cells, combination 1703880 an anti-programmed cell protein 1-antibody, such as ezabenlimab, may improve efficacy. This first-in-human phase Ia study (NCT05471856) is evaluating plus ezabenlimab patients with advanced solid tumors. The utilizes innovative lead-in design; all receive monotherapy Cycle therapy from 2. primary endpoint dose-limiting toxicities during the maximum tolerated dose evaluation period. Results will inform future development for treatment metastatic or recurrent malignancies.Clinical Trial number: NCT05471856.

Язык: Английский

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Genome-wide CRISPR screening identifies PHF8 as an effective therapeutic target for KRAS- or BRAF-mutant colorectal cancers

Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)

Опубликована: Фев. 25, 2025

Abstract Background Mutations in KRAS and BRAF genes are prevalent colorectal cancer (CRC), which strikingly promote tumorigenesis lead to poor response a variety of treatments including immunotherapy by activating the MAPK/ERK pathway. Thus, there is an urgent need discover effective therapeutic targets strategies. Methods CRISPR-Cas9 lentiviral knockout library was used screen suppressors anti-PD1 immunotherapy. Bioinformatic analysis analyze correlation between PHF8 expression immune indicators CRC. In vitro vivo experiments were utilized determine effects on indexes malignant phenotypes CRC cells. qRT-PCR, western blotting, immunohistochemical (IHC) staining, chromatin immunoprecipitation (ChIP)-qPCR assays regulatory PD-L1, KRAS, BRAF, c-Myc effect c-Myc/miR-22-3p signaling axis Results This study identified histone lysine demethylase as negative regulator for efficacy therapy found that it highly expressed CRCs strongly associated with patient survival. Functional studies showed played oncogenic role KRAS- or BRAF-mutant cells, but not wild-type ones. Mechanistically, up-regulated increasing levels transcriptional activation marks H3K4me3 H3K27ac decreasing repression mark H3K9me2 within their promoter regions, promoting escape tumor progression. Besides, our data also demonstrated form positive feedback loop. Targeting substantially improved inhibited Conclusion Our demonstrate may be target CRCs.

Язык: Английский

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Cancer-associated fibroblasts in non-small cell lung cancer: Recent advances and future perspectives

Cancer Letters, Год журнала: 2021, Номер 514, С. 38 - 47

Опубликована: Май 18, 2021

Язык: Английский

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Clinical benefits of PD-1/PD-L1 inhibitors in patients with metastatic colorectal cancer: a systematic review and meta-analysis

World Journal of Surgical Oncology, Год журнала: 2022, Номер 20(1)

Опубликована: Март 24, 2022

Immunotherapy for colorectal cancer has developed rapidly in the past decade. Many high-quality clinical trials examining application of PD-1/PD-L1 inhibitors patients with metastatic (mCRC) have been conducted recent years. However, benefits, including efficacy and safety these treatments against mCRC, remain controversial. Hence, we this meta-analysis on benefits mCRC.We searched online databases MEDLINE, Embase, Cochrane Library, Web Science, from inception to January 4, 2021. The outcomes related were extracted analyzed. Subgroup analyses according categories dMMR-MSI-H (tumors mismatch repair deficiency high levels microsatellite instability) ≥ 5% vs. < 5%, monotherapy combination therapy, PD-1 PD-L1 inhibitors, nivolumab pembrolizumab.Fourteen studies 1129 subjects included our systematic review. overall complete response (CR), partial (PR), stable disease (SD), progression (PD) rates 0.01 (95% CI 0.00-0.04), 0.04 0.05-0.26), 0.27 0.22-0.32), 0.44 0.30-0.58), respectively. objective rate (ORR) control (DCR) 0.16 (95%CI 0.06-0.31) 0.50 0.35-0.65), adverse events (AEs) severe responses (SAEs) 0.84 0.72-0.92) 0.30 0.20-0.41), ORRs subgroups 0.40 0.30-0.51) 0.00-0.09), respectively.PD-1/PD-L1 produced encouraging treatment mCRC. They actually influenced by present state mCRC therapy pMMR-MSI-L Nevertheless, additional multi-center prospective are still expected.We registered study International Prospective Register Systematic Reviews (PROSPERO), registration number is CRD42021249601 .

Язык: Английский

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Molecular Farming of Pembrolizumab and Nivolumab

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(12), С. 10045 - 10045

Опубликована: Июнь 12, 2023

Immune checkpoint inhibitors (ICIs) are a class of immunotherapy agents capable alleviating the immunosuppressive effects exerted by tumorigenic cells. The programmed cell death protein 1 (PD-1)/programmed death-ligand (PD-L1) immune is one most ubiquitous checkpoints utilized cells for evasion inducing apoptosis and inhibiting proliferation cytokine production T lymphocytes. Currently, frequently used ICIs targeting PD-1/PD-L1 include monoclonal antibodies (mAbs) pembrolizumab nivolumab that bind to PD-1 on lymphocytes inhibit interaction with PD-L1 However, costly, thus their accessibility limited in low- middle-income countries (LMICs). Therefore, it essential develop novel biomanufacturing platforms reducing cost these two therapies. Molecular farming such platform utilizing plants mAb production, has been demonstrated be rapid, low-cost, scalable can potentially implemented LMICs diminish exorbitant prices, ultimately leading significant reduction cancer-related mortalities within countries.

Язык: Английский

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