Intratumor microbiome in cancer progression: current developments, challenges and future trends

Biomarker Research, Journal Year: 2022, Volume and Issue: 10(1)

Published: May 31, 2022

Abstract Cancer is a complicated disease attributed to multifactorial changes, which causes difficulties with treatment strategies. Various factors have been regarded as the main contributors, and infectious etiological recently attracted interest. Several microbiomes contribute carcinogenesis, cancer progression, modulating by inducing cancerous epithelial cells chronic inflammation. Most of our knowledge on role microbiota in tumor oncogenesis clinical efficiency associated intestinal microbiome. However, compelling evidence has also confirmed contribution intratumor microbiome cancer. Indeed, findings samples, animal models, studies vitro revealed that many promote tumorigenesis immune evasion. In addition, participates regulating response even affects outcomes treatment. This review summarizes interplay between cancer, focusing mechanism initiation, potential applications therapy.

Language: Английский

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A review of treatment options employed in relapsed/refractory AML

Hematology, Journal Year: 2023, Volume and Issue: 28(1)

Published: April 10, 2023

Introduction: Acute myeloid leukemia [AML] is a heterogenous group of primary hematopoietic neoplasms arising from precursor cells. Up to 50% patients failed achieve remission with initial therapy and go on develop refractory AML. Whenever possible, enrollment in clinical trial view the paucity evidence surrounding clearly superior treatment modality recommended, which provides best chance for cure post allogeneic stem cell transplantation [HCT], much everyday decision-making relapsed/refractory (R/R) AML choice least toxic regimen that could enable prompt HCT.Discussion: We discuss variety modalities employed R/R setting beginning traditional cytotoxic regimens. then turn our attention targeted therapies have shown efficacy specific patient populations such as IDH inhibitors FLT3 lastly, we immunotherapeutic agents setting, CD33 bispecific antibodies.Conclusion: It appears increasingly clear approaching homogenous disease entity unsatisfactory variations factors cytogenetic molecular markers, age, severity at presentation; all contribute significantly heterogeneity disease. Moving forward, treating would likely require tailored following advances technology profiling, drug sensitivity resistance testing.

Language: Английский

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Advances in mRNA therapeutics for cancer immunotherapy: From modification to delivery

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 199, P. 114973 - 114973

Published: June 25, 2023

Language: Английский

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Xaluritamig, a STEAP1 × CD3 XmAb 2+1 Immune Therapy for Metastatic Castration-Resistant Prostate Cancer: Results from Dose Exploration in a First-in-Human Study

Cancer Discovery, Journal Year: 2023, Volume and Issue: 14(1), P. 76 - 89

Published: Oct. 20, 2023

Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis STEAP1-expressing cancer cells, such as those in advanced cancer. This first-in-human study reports monotherapy dose exploration for patients with metastatic castration-resistant (mCRPC), primarily taxane pretreated. Ninety-seven received ≥1 intravenous ranging from 0.001 2.0 mg weekly or every 2 weeks. MTD was identified 1.5 i.v. via 3-step dose. The most common treatment-related adverse events were cytokine release syndrome (CRS; 72%), fatigue (45%), and myalgia (34%). CRS occurred during cycle improved premedication step dosing. Prostate-specific (PSA) RECIST responses across cohorts encouraging [49% PSA50; 24% objective response rate (ORR)], greater frequency at target doses ≥0.75 (59% 41% ORR). novel immunotherapy that has shown results supporting further development.

Language: Английский

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Decoding the Complexity of Immune–Cancer Cell Interactions: Empowering the Future of Cancer Immunotherapy

Cancers, Journal Year: 2023, Volume and Issue: 15(16), P. 4188 - 4188

Published: Aug. 21, 2023

The tumor and microenvironment (TME) consist of a complex network cells, including malignant, immune, fibroblast, vascular which communicate with each other. Disruptions in cell–cell communication within the TME, caused by multitude extrinsic intrinsic factors, can contribute to tumorigenesis, hinder host immune system, enable evasion. Understanding addressing intercellular miscommunications TME are vital for combating these processes. effectiveness immunotherapy heterogeneous response observed among patients be attributed intricate cellular between cells cancer cells. To unravel interactions, various experimental, statistical, computational techniques have been developed. These include ligand–receptor analysis, proximity labeling approaches, imaging-based methods, provide insights into distorted interactions TME. By characterizing we enhance design strategies. In this review, present recent advancements field mapping communication, particular focus on immune–tumor interactions. modeling identify critical factors develop strategies improve overcome treatment resistance.

Language: Английский

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Mechanisms of immune modulation in the tumor microenvironment and implications for targeted therapy

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: June 22, 2023

The efficacy of cancer therapies is limited to a great extent by immunosuppressive mechanisms within the tumor microenvironment (TME). Numerous immune escape have been identified. These include not only processes associated with tumor, or stromal cells, but also humoral, metabolic, genetic and epigenetic factors TME. identification has enabled development small molecules, nanomedicines, checkpoint inhibitors, adoptive cell that can reprogram TME shift host response towards promoting an antitumor effect. approaches translated into series breakthroughs in therapies, some which already implemented clinical practice. In present article authors provide overview most important immunosuppression implications for targeted against different cancers.

Language: Английский

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Using quantitative systems pharmacology modeling to optimize combination therapy of anti-PD-L1 checkpoint inhibitor and T cell engager

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

Published: June 20, 2023

Although immune checkpoint blockade therapies have shown evidence of clinical effectiveness in many types cancer, the outcome trials shows that very few patients with colorectal cancer benefit from treatments inhibitors. Bispecific T cell engagers (TCEs) are gaining popularity because they can improve patients' immunological responses by promoting activation. The possibility combining TCEs inhibitors to increase tumor response and patient survival has been highlighted preclinical outcomes. However, identifying predictive biomarkers optimal dose regimens for individual combination therapy remains one main challenges. In this article, we describe a modular quantitative systems pharmacology (QSP) platform immuno-oncology includes specific processes immune-cancer interactions was created based on published data cancer. We generated virtual cohort model conduct

Language: Английский

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Prostate cancer immunotherapy: Improving clinical outcomes with a multi-pronged approach

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(10), P. 101199 - 101199

Published: Sept. 21, 2023

Cancer immunotherapy has gained traction in recent years owing to remarkable tumor clearance some patients. Despite the notable success of immune checkpoint blockade (ICB) multiple malignancies, engagement system for targeted prostate cancer (PCa) therapy is still its infancy. Multiple factors contribute limited response, including heterogeneity PCa, cold microenvironment, and a low number neoantigens. Significant effort being invested improving immune-based PCa therapies. This review summary status treating with discussion modalities, vaccines, adoptively transferred T cells, bispecific cell engagers, which are undergoing clinical trials. In addition, this also focuses on emerging mechanism-based small-molecule tyrosine kinase inhibitors modulatory properties that, either as single agents or combination other immunotherapies, have potential improve outcomes.

Language: Английский

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The enhanced antitumor activity of bispecific antibody targeting PD-1/PD-L1 signaling

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 12, 2024

Abstract The programmed cell death 1 (PD-1) signaling pathway, a key player in immune checkpoint regulation, has become focal point cancer immunotherapy. In the context of cancer, upregulated PD-L1 on tumor cells can result T exhaustion and evasion, fostering progression. advent PD-1/PD-L1 inhibitor demonstrated clinical success by unleashing from exhaustion. Nevertheless, challenges such as resistance adverse effects have spurred exploration innovative strategies, with bispecific antibodies (BsAbs) emerging promising frontier. BsAbs offer multifaceted approach to immunotherapy simultaneously targeting other regulatory molecules. We focus recent advancements therapy particular emphasis development potential BsAbs, especially solid tumors. Various BsAb products PD-1 are discussed, highlighting their unique mechanisms action therapeutic potential. Noteworthy examples include anti-TGFβ × PD-L1, anti-CD47 anti-VEGF anti-4-1BB anti-LAG-3 anti-PD-1 CTLA-4 BsAbs. Besides, we summarize ongoing studies evaluating efficacy safety these agents. By unraveling intricacies microenvironment harnessing synergistic anti-PD-1/PD-L1 there exists elevate precision immunotherapy, ultimately enabling personalized treatment strategies tailored individual patient profiles.

Language: Английский

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A Phase I Study of Acapatamab, a Half-life Extended, PSMA-Targeting Bispecific T-cell Engager for Metastatic Castration-Resistant Prostate Cancer

Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 30(8), P. 1488 - 1500

Published: Feb. 1, 2024

Abstract Purpose: Safety and efficacy of acapatamab, a prostate-specific membrane antigen (PSMA) x CD3 bispecific T-cell engager were evaluated in first-in-human study metastatic castration-resistant prostate cancer (mCRPC). Patients Methods: with mCRPC refractory to androgen receptor pathway inhibitor therapy taxane-based chemotherapy received target acapatamab doses ranging from 0.003 0.9 mg dose exploration (seven levels) 0.3 (recommended phase II dose) expansion intravenously every 2 weeks. (primary objective), pharmacokinetics, antitumor activity (secondary objectives) assessed. Results: In all, 133 patients (dose exploration, n = 77; expansion, 56) acapatamab. Cytokine release syndrome (CRS) was the most common treatment-emergent adverse event seen 97.4% 98.2% respectively; grade ≥ 3 23.4% 16.1%, respectively. Most CRS events treatment cycle 1; incidence severity decreased at/beyond 2. confirmed (PSA) responses (PSA50) 30.4% radiographic partial 7.4% (Response Evaluation Criteria Solid Tumors 1.1). Median PSA progression-free survival (PFS) 3.3 months [95% confidence interval (CI): 3.0–4.9], PFS per Prostate Cancer Clinical Trials Working Group 3.7 (95% CI: 2.0–5.4). Acapatamab induced activation increased cytokine production several-fold within 24 hours initiation. Treatment-emergent antidrug antibodies detected 55% impacted serum exposures 36% expansion. Conclusions: safe tolerated had manageable profile. Preliminary signs limited durable observed. demonstrated pharmacokinetic pharmacodynamic activity.

Language: Английский

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