Bispecific antibody drug conjugates: Making 1+1&gt;2

Gu, Yilin; Wang, Zhijia; Wang, Yuxi

doi:10.1016/j.apsb.2024.01.009

Cited by 12 publications

(2 citation statements)

References 236 publications

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“…ADCs with dual payloads hold therapeutic potential in overcoming heterogeneity and drug resistance ( Yamazaki et al, 2021 ). Bispecific ADCs combining the antitumor mechanisms of ADCs with the multifunctionality of bispecific antibodies can address the clinical challenges in ADC development ( Gu et al, 2024 ). Furthermore, dual-targeting agents could include not only bispecific antibodies but also novel bispecific molecules ( An et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of antibody–drug conjugates in the treatment of urothelial cell carcinoma: a systematic review and meta-analysis of prospective clinical trials

Ren,

Chen,

Bai

et al. 2024

Front. Pharmacol.

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Introduction: Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody–drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases.Methods: A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses.Results: Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%).Conclusion: The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC.Systematic review registration:https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of antibody–drug conjugates in the treatment of urothelial cell carcinoma: a systematic review and meta-analysis of prospective clinical trials

Ren,

Chen,

Bai

et al. 2024

Front. Pharmacol.

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“…ADCs with dual payloads hold therapeutic potential in overcoming heterogeneity and drug resistance (Yamazaki et al, 2021). Bispecific ADCs combining the antitumor mechanisms of ADCs with the multifunctionality of bispecific antibodies can address the clinical challenges in ADC development (Gu et al, 2024). Furthermore, dual-targeting agents could include not only bispecific antibodies but also novel bispecific molecules (An et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

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The Evolution of Antibody‐Drug Conjugates: Toward Accurate DAR and Multi‐specificity

Dong,

Wang,

Cao

2024

ChemMedChem

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Antibody‐drug conjugates (ADCs) are consisted of antibodies, linker and payloads. They offer targeted delivery of potent cytotoxic drugs to tumor cells, minimizing off‐target effects. However, the therapeutic efficacy of ADCs is compromised by the heterogeneity in the drug‐to‐antibody ratio (DAR), which impacts both cytotoxicity and pharmacokinetics (PK). Additionally, the emergence of drug resistance poses significant challenges to the clinical advancement of ADCs. To overcome these limitations, a variety of strategies have been developed, including the design of multi‐specific drugs with accurate DAR. This review critically summarized the current challenges faced by ADCs, categorizing key issues and evaluating various innovative solutions. We provide an in‐depth analysis of the latest methodologies for achieving homogeneous DAR and explore the design strategies for multi‐specific drugs aimed at combating drug resistance. Our discussion offers insights into the progress made in refining ADC technologies, with a focus on enhancing therapeutic outcomes.

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Bispecific antibody drug conjugates: Making 1+1>2

Cited by 12 publications

References 236 publications

Efficacy and safety of antibody–drug conjugates in the treatment of urothelial cell carcinoma: a systematic review and meta-analysis of prospective clinical trials

Efficacy and safety of antibody–drug conjugates in the treatment of urothelial cell carcinoma: a systematic review and meta-analysis of prospective clinical trials

DataSheet1.pdf

The Evolution of Antibody‐Drug Conjugates: Toward Accurate DAR and Multi‐specificity

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