Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer

JAMA, Journal Year: 2023, Volume and Issue: 330(21), P. 2064 - 2064

Published: Dec. 5, 2023

Importance Gastric and gastroesophageal junction cancers are diagnosed in more than 1 million people worldwide annually, few effective treatments available. Sintilimab, a recombinant human IgG4 monoclonal antibody that binds to programmed cell death (PD-1), combination with chemotherapy, has demonstrated promising efficacy. Objective To compare overall survival of patients unresectable locally advanced or metastatic gastric who were treated sintilimab chemotherapy vs placebo chemotherapy. Also compared subset PD ligand (PD-L1) combined positive score (CPS) 5 (range, 1-100). Design, Setting, Participants Randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 62 hospitals China enrolled 650 adenocarcinoma between January 3, 2019, August 5, 2020. Final follow-up occurred on June 20, 2021. Interventions Patients randomized 1:1 either (n = 327) 323) capecitabine oxaliplatin (the XELOX regimen) every weeks for maximum 6 cycles. Maintenance therapy plus continued up 2 years. Main Outcomes Measures The primary end point was time from randomization. Results Of the (mean age, 59 years; 483 [74.3%] men), 327 323 Among patients, 397 (61.1%) had tumors PD-L1 CPS more; 563 (86.6%) discontinued study treatment 388 (59.7%) died; patient (<0.1%) lost follow-up. all improved (median, 15.2 12.3 months; stratified hazard ratio [HR], 0.77 [95% CI, 0.63-0.94]; P .009). more, 18.4 12.9 HR, 0.66 0.50-0.86]; .002). most common grade higher treatment-related adverse events decreased platelet count (sintilimab, 24.7% placebo, 21.3%), neutrophil 20.1% 18.8%), anemia 12.5% 8.8%). Conclusions Relevance first-line significantly placebo. Trial Registration ClinicalTrials.gov Identifier: NCT03745170

Language: Английский

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A comprehensive overview on antibody-drug conjugates: from the conceptualization to cancer therapy

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 18, 2023

Antibody-Drug Conjugates (ADCs) represent an innovative class of potent anti-cancer compounds that are widely used in the treatment hematologic malignancies and solid tumors. Unlike conventional chemotherapeutic drug-based therapies, mainly associated with modest specificity therapeutic benefit, three key components form ADC (a monoclonal antibody bound to a cytotoxic drug via chemical linker moiety) achieve remarkable improvement terms targeted killing cancer cells and, while sparing healthy tissues, reduction systemic side effects caused by off-tumor toxicity. Based on their beneficial mechanism action, 15 ADCs have been approved date market approval Food Drug Administration (FDA), European Medicines Agency (EMA) and/or other international governmental agencies for use clinical oncology, hundreds undergoing evaluation preclinical phases. Here, our aim is provide comprehensive overview features revolving around strategy including structural targeting properties, role tumor microenvironment review providing discussion regarding toxicity profile, manifestations novel combination therapies. Finally, we briefly pathological contexts information manufacturing analytical characterization.

Language: Английский

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PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughs in cancer treatment

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Dec. 1, 2023

PD-1 (Programmed Cell Death Protein-1) and PD-L1 Ligand-1) play a crucial role in regulating the immune system preventing autoimmunity. Cancer cells can manipulate this system, allowing them to escape detection promote tumor growth. Therapies targeting PD-1/PD-L1 pathway have transformed cancer treatment demonstrated significant effectiveness against various types. This study delves into structure signaling dynamics of its ligands PD-L1/PD-L2, diverse inhibitors their efficacy, resistance observed some patients. Furthermore, explored challenges associated with inhibitor approach. Recent advancements combination immunotherapy chemotherapy, radiation, surgical procedures enhance patient outcomes also been highlighted. Overall, offers an in-depth overview significance future implications oncology.

Language: Английский

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Exploring the dynamic interplay between cancer stem cells and the tumor microenvironment: implications for novel therapeutic strategies

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Oct. 2, 2023

Cancer stem cells (CSCs) have emerged as key contributors to tumor initiation, growth, and metastasis. In addition, CSCs play a significant role in inducing immune evasion, thereby compromising the effectiveness of cancer treatments. The reciprocal communication between microenvironment (TME) is observed, with TME providing supportive niche for CSC survival self-renewal, while CSCs, turn, influence polarization persistence TME, promoting an immunosuppressive state. Consequently, these interactions hinder efficacy current therapies, necessitating exploration novel therapeutic approaches modulate target CSCs. this review, we highlight intricate strategies employed by evade surveillance develop resistance therapies. Furthermore, examine dynamic interplay shedding light on how interaction impacts progression. Moreover, provide overview advanced that specifically which hold promise future clinical translational studies treatment.

Language: Английский

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Prognostic Value of Neutrophil-to-Eosinophil Ratio (NER) in Cancer: A Systematic Review and Meta-Analysis

Cancers, Journal Year: 2024, Volume and Issue: 16(21), P. 3689 - 3689

Published: Oct. 31, 2024

The identification of reliable prognostic biomarkers is crucial for optimizing cancer treatment strategies, especially in the era personalized medicine. This systematic review and meta-analysis evaluate significance neutrophil-to-eosinophil ratio (NER) various types, with a focus on its association overall survival (OS) progression-free (PFS).

Language: Английский

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The role of PD-1 signaling in health and immune-related diseases

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 16, 2023

Programmed cell death 1 receptor (PD-1) and its ligands constitute an inhibitory pathway to mediate the mechanism of immune tolerance provide homeostasis. Significantly, binding partners PD-1 associated are diverse, which facilitates immunosuppression in cooperation with other checkpoint proteins. Accumulating evidence has demonstrated important immunosuppressive role axis tumor microenvironment autoimmune diseases. In addition, blockades have been approved treat various cancers, including solid tumors hematological malignancies. Here, we a comprehensive review pathway, focusing on structure expression PD-1, programmed ligand (PD-L1), 2 (PD-L2); diverse biological functions signaling health immune-related diseases (including immunity, autoimmunity, infectious transplantation allergy privilege); adverse events related PD-L1 inhibitors.

Language: Английский

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CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(10), P. 1089 - 1108

Published: Aug. 12, 2024

Abstract In the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers, demonstrating remarkable efficacy in relapsed/refractory hematological malignancies both pediatric and adult patients. CAR-natural killer (CAR-NK) complements CAR-T by offering several distinct advantages. CAR-NK cells do not require HLA compatibility exhibit low safety concerns. Moreover, are conducive to “off-the-shelf” therapeutics, providing significant logistic advantages over cells. Both have shown consistent results malignancies. However, their against solid tumors remains limited due various obstacles including tumor trafficking infiltration, well an immuno-suppressive microenvironment. this review, we discuss recent advances current challenges of immunotherapies, with specific focus on application tumors. We also analyze depth drawbacks compared highlight CAR optimization. Finally, explore future perspectives these adoptive highlighting increasing contribution cutting-edge biotechnological tools shaping next generation cellular immunotherapy.

Language: Английский

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Engineered Bio‐Based Hydrogels for Cancer Immunotherapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(21)

Published: Feb. 16, 2024

Immunotherapy represents a revolutionary paradigm in cancer management, showcasing its potential to impede tumor metastasis and recurrence. Nonetheless, challenges including limited therapeutic efficacy severe immune-related side effects are frequently encountered, especially solid tumors. Hydrogels, class of versatile materials featuring well-hydrated structures widely used biomedicine, offer promising platform for encapsulating releasing small molecule drugs, biomacromolecules, cells controlled manner. Immunomodulatory hydrogels present unique capability augmenting immune activation mitigating systemic toxicity through encapsulation multiple components localized administration. Notably, based on biopolymers have gained significant interest owing their biocompatibility, environmental friendliness, ease production. This review delves into the recent advances bio-based immunotherapy synergistic combinatorial approaches, highlighting diverse applications. It is anticipated that this will guide rational design field immunotherapy, fostering clinical translation ultimately benefiting patients.

Language: Английский

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Immune-mediated disease caused by climate change-associated environmental hazards: mitigation and adaptation

Frontiers in Science, Journal Year: 2024, Volume and Issue: 2

Published: April 4, 2024

Global warming and climate change have increased the pollen burden frequency intensity of wildfires, sand dust storms, thunderstorms, heatwaves—with concomitant increases in air pollution, heat stress, flooding. These environmental stressors alter human exposome trigger complex immune responses. In parallel, pollutants, allergens, other factors increase risks skin mucosal barrier disruption microbial dysbiosis, while a loss biodiversity reduced exposure to diversity impairs tolerogenic development. The resulting dysregulation is contributing an immune-mediated diseases such as asthma allergic diseases, autoimmune cancer. It now abundantly clear that multisectoral, multidisciplinary, transborder efforts based on Planetary Health One approaches (which consider dependence health environment natural ecosystems) are urgently needed adapt mitigate effects change. Key actions include reducing emissions improving quality (through fossil fuel use), providing safe housing (e.g., weatherization), diets (i.e., diversity) agricultural practices, increasing green spaces. There also pressing need for collaborative, multidisciplinary research better understand pathophysiology context New data science techniques, biomarkers, economic models should be used measure impact disease, inform mitigation adaptation efforts, evaluate their effectiveness. Justice, equity, diversity, inclusion (JEDI) considerations integral these address disparities

Language: Английский

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Immunotherapy in Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7517 - 7517

Published: July 9, 2024

Breast cancer is a disease encompassing spectrum of molecular subtypes and clinical presentations, each with distinct prognostic implications treatment responses. has traditionally been considered an immunologically "cold" tumor, unresponsive to immunotherapy. However, trials in recent years have found immunotherapy be efficacious therapeutic option for select patients. categorized into different ranging from the most common positive hormone receptor (HR+), human epidermal growth factor 2 (HER2)-negative type, less frequent HER2- breast triple-negative (TNBC), highlighting necessity tailored strategies aimed at maximizing patient outcomes. Despite notable progress early detection new modalities, remains second leading cause death USA. Moreover, decades, incidence rates increasing, especially women younger than age 50. This prompted exploration approaches address this trend, offering prospects Immunotherapy class agents that revolutionized landscape many cancers, namely melanoma, lung cancer, gastroesophageal amongst others. Though belatedly, entered armamentarium approval pembrolizumab combination chemotherapy (TNBC) neoadjuvant advanced settings, thereby paving path further research integration immune checkpoint inhibitors other cancer. Trials exploring various therapies harness power symbiosis chemotherapeutic are ongoing hopes improving response prolonging survival Biomarkers precise selection utilization remain cardinal currently under investigation, some biomarkers showing promise, such as Program Death Lignat-1 (PDL-1) Combined Positive Score, Tumor Mutation Burden (TMB), Infiltrating Lymphocytes (TILs). review will present current immunotherapy, particularly inhibitors, types

Language: Английский

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