Trends in nanobody radiotheranostics

European Journal of Nuclear Medicine and Molecular Imaging, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Язык: Английский

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Immunogenicity of cell death and cancer immunotherapy with immune checkpoint inhibitors

Cellular and Molecular Immunology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 10, 2024

While immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the clinical management of various malignancies, a large fraction patients are refractory to ICIs employed as standalone therapeutics, necessitating development combinatorial treatment strategies. Immunogenic cell death (ICD) inducers have attracted considerable interest partners for ICIs, at least in part owing their ability initiate tumor-targeting adaptive response. However, compared either approach alone, regimens involving ICD and not always shown superior activity. Here, we discuss accumulating evidence on therapeutic interactions between oncological settings, identify key factors that may explain discrepancies preclinical findings, propose strategies address existing challenges increase efficacy these combinations cancer.

Язык: Английский

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Engineering CAR‐T Therapeutics for Enhanced Solid Tumor Targeting

Advanced Materials, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Abstract Cancer immunotherapy, specifically Chimeric Antigen Receptor (CAR)‐T cell therapy, represents a significant breakthrough in treating cancers. Despite its success hematological cancers, CAR‐T exhibits limited efficacy solid tumors, which account for more than 90% of all Solid tumors commonly present unique challenges, including antigen heterogeneity and complex tumor microenvironment (TME). To address these, efforts are being made through improvements CAR design the development advanced validation platforms. While is limited, some types, such as neuroblastoma gastrointestinal have shown responsiveness to therapy recent clinical trials. In this review, it first examined both experimental computational strategies, protein engineering coupled with machine learning, developed enhance T specificity. The challenges methods associated delivery vivo reprogramming discussed. It also explored advancements engineered organoid systems, emerging high‐fidelity vitro models that closely mimic human TME serve platform discovery. Collectively, these innovative strategies offer potential revolutionize next generation ultimately paving way effective treatments tumors.

Язык: Английский

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Engineering synthetic phosphorylation signaling networks in human cells

Science, Год журнала: 2025, Номер 387(6729), С. 74 - 81

Опубликована: Янв. 2, 2025

Protein phosphorylation signaling networks have a central role in how cells sense and respond to their environment. We engineered artificial which reversible enzymatic cycles were assembled from modular protein domain parts wired together create synthetic circuits human cells. Our design scheme enabled model-guided tuning of circuit function the ability make diverse network connections; can be coupled upstream cell surface receptors enable fast-timescale sensing extracellular ligands, downstream connections regulate gene expression. cell-based cytokine controllers that dynamically suppress activated T work introduces generalizable approach allows user-defined sense-and-respond for biosensing therapeutic applications.

Язык: Английский

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The CD123 antibody–drug conjugate pivekimab sunirine exerts profound activity in preclinical models of pediatric acute lymphoblastic leukemia

HemaSphere, Год журнала: 2025, Номер 9(1)

Опубликована: Янв. 1, 2025

Antibody-drug conjugates (ADCs) combining monoclonal antibodies with cytotoxic payloads are a rapidly emerging class of immune-based therapeutics the potential to improve treatment cancer, including children relapse/refractory acute lymphoblastic leukemia (ALL). CD123, α subunit interleukin-3 receptor, is overexpressed in ALL and therapeutic target. Here, we show that pivekimab sunirine (PVEK), recently developed ADC comprising CD123-targeting antibody, G4723A, payload, DGN549, was highly effective vivo against large panel pediatric patient-derived xenograft (PDX) models (n = 39). PVEK administered once weekly for 3 weeks resulted median event-free survival (EFS) 57.2 days across all PDXs. CD123 mRNA protein expression significantly higher B-lineage 65) compared T-lineage 25) PDXs (p < 0.0001), mice engrafted achieved longer EFS than those 0.0001). also significant clearance human cells hematolymphoid organs B-ALL Notably, our results showed no direct correlation between mouse EFS, indicating necessary but not sufficient activity. Importantly, PDX very high cell surface resistant treatment, failed internalize G4723A antibody while remaining sensitive suggesting novel mechanism resistance. In conclusion, supporting its clinical translation ALL.

Язык: Английский

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Prodrug-based bispecific antibodies for cancer therapy: advances and future directions

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 22, 2025

Bispecific antibodies represent an innovative paradigm in cancer therapy, offering broader therapeutic potential compared to conventional monoclonal antibodies. To increase tumor selectivity while mitigating off-target effects normal tissues, the concept of prodrug-based bispecific has emerged. This review delineates various mechanisms underlying action antibodies, including protease-mediated activation, steric hindrance release via proteolytic processing, activation by soluble factors, conditional assembly, and chain exchange-mediated activation. We also address critical challenges that must be overcome optimize development clinical application these sophisticated agents.

Язык: Английский

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Living Bacteria: A New Vehicle for Vaccine Delivery in Cancer Immunotherapy

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 2056 - 2056

Опубликована: Фев. 26, 2025

Cancer vaccines, aimed at evolving the human immune system to eliminate tumor cells, have long been explored as a method of cancer treatment with significant clinical potential. Traditional delivery systems face challenges in directly targeting cells and delivering adequate amounts antigen due hostile microenvironment. Emerging evidence suggests that certain bacteria naturally home on tumors modulate antitumor immunity, making bacterial vectors promising vehicle for precision vaccines. Live vehicles offer several advantages, including colonization, precise drug delivery, stimulation, them compelling option immunotherapy. In this review, we explore mechanisms action behind living bacteria-based recent progress popular chassis, strategies specific payload biocontainment ensure safety. These approaches will lay foundation developing an affordable, widely applicable vaccine system. This review also discusses future opportunities harnessing bacterial-based vaccines enhanced therapeutic outcomes treatment.

Язык: Английский

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Next-Generation Therapeutic Antibodies for Cancer Treatment: Advancements, Applications, and Challenges

Molecular Biotechnology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 2, 2024

Язык: Английский

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Single-Domain Antibodies as Antibody–Drug Conjugates: From Promise to Practice—A Systematic Review

Cancers, Год журнала: 2024, Номер 16(15), С. 2681 - 2681

Опубликована: Июль 27, 2024

Background: Antibody–drug conjugates (ADCs) represent potent cancer therapies that deliver highly toxic drugs to tumor cells precisely, thus allowing for targeted treatment and significantly reducing off-target effects. Despite their effectiveness, ADCs can face limitations due acquired resistance potential side Objectives: This study focuses on advances in various ADC components improve both the efficacy safety of these agents, includes analysis several novel formats. work assesses whether unique features VHHs—such as small size, enhanced tissue penetration, stability, cost-effectiveness—make them a viable alternative conventional antibodies reviews current status development. Methods: Following PRISMA guidelines, this focused VHHs ADCs, examining advancements prospects from 1 January 2014 30 June 2024. Searches were conducted PubMed, Cochrane Library, ScienceDirect LILACS using specific terms related single-domain antibodies. Retrieved articles rigorously evaluated, excluding duplicates non-qualifying studies. The selected peer-reviewed analyzed quality synthesized highlight advancements, methods, payloads, future directions research. Results: offer significant advantages drug conjugation over smaller size structure, which enhance penetration enable access previously inaccessible epitopes. Their superior solubility, manufacturability facilitate cost-effective production expand range targetable antigens. Additionally, some naturally cross blood–brain barrier or be easily modified favor making promising targeting brain tumors metastases. Although no VHH–drug (nADC nanoADC) are currently clinical arena, preclinical studies have explored methods linkers. Conclusions: While transforming treatment, mechanisms associated toxicities challenge traditional views bioavailability vary with different types. Severe toxicities, often linked compound instability, effects, nonspecific blood cell interactions, need better understanding. Conversely, rapid distribution, clearance could advantageous, potentially toxicity by minimizing prolonged exposure. These attributes make strong candidates next generation enhancing safety.

Язык: Английский

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Targeted and cytotoxic inhibitors used in the treatment of lung cancers

Pharmacological Research, Год журнала: 2024, Номер unknown, С. 107465 - 107465

Опубликована: Окт. 1, 2024

Язык: Английский

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