Anti-PD-1/PD-L1 therapy for colorectal cancer: Clinical implications and future considerations

Translational Oncology, Journal Year: 2023, Volume and Issue: 40, P. 101851 - 101851

Published: Dec. 1, 2023

Colorectal cancer (CRC) is the third most prevalent in world. The PD-1/PD-L1 pathway plays a crucial role modulating immune response to cancer, and PD-L1 expression has been observed tumor cells within microenvironment of CRC. Thus, immunotherapy drugs, specifically checkpoint inhibitors, have developed target signaling pathway, thereby inhibiting interaction between PD-1 restoring T-cell function cells. However, emergence resistance mechanisms can reduce efficacy these treatments. To counter this, monoclonal antibodies (mAbs) used improve CRC mAbs such as nivolumab pembrolizumab are currently approved for treatment. These impede receptors, including PD-1/PD-L1, their combination therapy shows promise treatment advanced This review presents concise overview use blockade therapeutic strategy using therapies. Additionally, this article outlines an suppressor well potential advantages administering inflammatory agents Finally, analyzes outcomes clinical trials examine challenges anti-PD-1/PD-L1 resistance.

Language: Английский

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Enhancing cancer immunotherapy: Exploring strategies to target the PD-1/PD-L1 axis and analyzing the associated patent, regulatory, and clinical trial landscape

European Journal of Pharmaceutics and Biopharmaceutics, Journal Year: 2024, Volume and Issue: 200, P. 114323 - 114323

Published: May 15, 2024

Language: Английский

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PD‐L1 Immune Checkpoint Targeted Photoactivable Liposomes (iTPALs) Prime the Stroma of Pancreatic Tumors and Promote Self‐Delivery

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(19)

Published: Feb. 7, 2024

Desmoplasia in pancreatic ductal adenocarcinoma (PDAC) limits the penetration and efficacy of therapies. It has been previously shown that photodynamic priming (PDP) using EGFR targeted photoactivable multi-inhibitor liposomes remediates desmoplasia PDAC doubles overall survival. Here, bifunctional PD-L1 immune checkpoint (iTPALs) mediate both PDP blockade are presented. iTPALs also improve phototoxicity cells induce immunogenic cell death. reduces collagen density, thereby promoting self-delivery by 5.4-fold hydrogels, 2.4-fold syngeneic CT1BA5 murine tumors. tumor fibroblast content 39.4%. Importantly, block PD-1/PD-L1 more efficiently than free α-PD-L1 antibodies. Only a single sub-curative dose provides 54.1% growth inhibition prolongs survival mice 42.9%. Overall directly correlates with extent iTPAL following (Pearson's r = 0.670, p 0.034), while no relationship is found for sham non-specific IgG constructs activated light. When applied over multiple cycles, as typical therapy, promises to offer durable delay significant benefit patients, especially when used promote integrated chemo-immunotherapy regimens.

Language: Английский

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A comprehensive review of immune checkpoint inhibitors for cancer treatment

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 143, P. 113365 - 113365

Published: Oct. 23, 2024

Language: Английский

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Exploring the Potential of Nanocarriers for Cancer Immunotherapy: Insights into Mechanism, Nanocarriers, and Regulatory Perspectives

ACS Applied Bio Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Immunotherapy is a cutting-edge approach that leverages sophisticated technology to target tumor-specific antibodies and modulate the immune system eradicate cancer enhance patients' quality of life. Bioinformatics genetic science advancements have made it possible diagnose treat patients using immunotherapy technology. However, current immunotherapies against limited clinical benefits due cancer-associated antigens, which often fail interact with cells exhibit insufficient therapeutic targeting unintended side effects. To surmount this challenge, nanoparticle systems emerged as potential strategy for transporting immunotherapeutic agents activating combat tumors. Consequently, process potentially generates an antigen-specific T response effectively suppresses growth. Furthermore, nanoplatforms high specificity, efficacy, diagnostic potential, imaging capabilities, making them promising tools treatment. informative paper delves into various available immunotherapies, including CAR therapy checkpoint blockade, cytokines, vaccines, monoclonal antibodies. concept theragnostic nanotechnology, integrates diagnostics more personalized treatment therapy. Additionally, covers different nanocarrier systems, marketed products, trials, regulatory considerations, future prospects immunotherapy.

Language: Английский

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Plant-derived Pembrolizumab in conjugation with IL-15Rα-IL-15 complex shows effective anti-tumor activity

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0316790 - e0316790

Published: Jan. 14, 2025

Anti-programmed cell death 1 (PD-1) monoclonal antibodies (mAbs) have proven to be effective in treating various cancers, including colorectal, lung, and melanoma. Despite their clinical success, some patients develop resistance mAbs, requiring co-treatments with radio- or chemotherapy. Interleukin-15 (IL-15) is an immunostimulatory cytokine that promotes immune production proliferation. It has been combined mAbs other immunotherapies improve efficacy reduce side effects. Fusion of anti-PD-1 mAb IL-15 streamlines drug administration management. In this study, we developed a prototype by conjugating the receptor subunit alpha (IL-15Rα) complex C-terminus Pembrolizumab (Pembrolizumab-IL-15Rα-IL15) using plant molecular farming for production. LC-MS revealed presence N -glycans (GnGnXF, GnXF Man9GlcNAc2) on molecule, which may affect receptor-binding avidity. However, ELISA demonstrated comparable binding Pembrolizumab-IL-15Rα-IL15 human PD-1 protein as commercial Pembrolizumab. mouse anti-cancer (3 mg kg -1 ) exhibited slightly improved tumor-growth inhibition, reducing tumor size 94% compared (5 83% reduction, regardless statistically significant difference. conclusion, Pembrolizumab-IL-15Rα-IL-15 was successfully produced shows promise addressing enhancing immunomodulatory effects payload.

Language: Английский

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Ferroptosis: CD8+T cells’ blade to destroy tumor cells or poison for self-destruction

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 1, 2025

Abstract Ferroptosis represents an emerging, iron-dependent form of cell death driven by lipid peroxidation. In recent years, it has garnered significant attention in the realm cancer immunotherapy, particularly studies involving immune checkpoint inhibitors. This not only enhances our comprehension tumor microenvironment but is also considered a promising therapeutic strategy to address resistance, investigate activation mechanisms, and facilitate development vaccines. The combination immunotherapy with ferroptosis provides innovative targets fresh perspectives for advancing treatment. Nevertheless, cells appear possess wider array evasion strategies compared CD8 + T cells, which have been conclusively shown be more vulnerable ferroptosis. Furthermore, TME can create favorable environment survival invasion. Under this premise, both inducing inhibiting will impact antitumor immunity some extent, even make final result run counter purpose. paper systematically elucidates dual-edged sword role process briefly outlining complexity within TME. It explores potential side effects associated ferroptosis-inducing therapies critically considers combined application ferroptosis-based ICIs. highlights current challenges faced approach points out future directions development.

Language: Английский

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Heterogeneity induced GZMA-F2R communication inefficient impairs antitumor immunotherapy of PD-1 mAb through JAK2/STAT1 signal suppression in hepatocellular carcinoma

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(3)

Published: March 7, 2022

Abstract Tumor heterogeneity has been associated with immunotherapy and targeted drug resistance in hepatocellular carcinoma (HCC). However, communications between tumor cytotoxic cells are poorly understood to date. In the present study, thirty-one clusters of were discovered tissues adjacent through single-cell sequencing. Moreover, quantity function exhaustion was observed be induced tumors by TCR apoptosis signal pathways. Furthermore, granzyme failure HCC patients. Importantly, GZMA secreted demonstrated interact F2R expressed both vivo vitro. This interaction suppression T cell-mediated killing via activation JAK2/STAT1 signaling pathway. Mechanistically, promoted under mediating effect LDPRSFLL motif at N-terminus F2R, which interacted GZMA. addition, positively correlated PD-1 PD-L1 tissues, while expressions mAb-induced mouse model Finally, patients, a low expression aggressive clinicopathological characteristics poor prognosis. Collectively, GZMA-F2R communication inefficient induces deficient mAb therapy provide completely novel strategy for

Language: Английский

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Tumor Microenvironment Immunosuppression: A Roadblock to CAR T-Cell Advancement in Solid Tumors

Cells, Journal Year: 2022, Volume and Issue: 11(22), P. 3626 - 3626

Published: Nov. 16, 2022

Chimeric antigen receptor (CAR) T cells are an exciting advancement in cancer immunotherapy, with striking success hematological cancers. However, solid tumors, the unique immunosuppressive elements of tumor microenvironment (TME) contribute to failure CAR cells. This review discusses cell populations, cytokine/chemokine profile, and metabolic TME. TME causes T-cell exhaustion influences successfully infiltrate tumors. Recent advances development, which seek overcome aspects immunosuppression, also reviewed. Novel discoveries overcoming limitations may lead

Language: Английский

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Aberrant N-glycosylation in cancer: MGAT5 and β1,6-GlcNAc branched N-glycans as critical regulators of tumor development and progression

Cellular Oncology, Journal Year: 2023, Volume and Issue: 46(3), P. 481 - 501

Published: Jan. 23, 2023

Language: Английский

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