3D Models as a Tool to Assess the Anti-Tumor Efficacy of Therapeutic Antibodies: Advantages and Limitations

Guzzeloni, Virginia; Veschini, Lorenzo; Pedica, Federica; Ferrero, Elisabetta; Ferrarini, Marina

doi:10.3390/antib11030046

Cited by 5 publications

(5 citation statements)

References 117 publications

(199 reference statements)

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“…In comparison to PDX models, PDE, by maintaining the phenotype and TME of the individual tumor, may provide a realistic environment to assess the functional ex vivo response to drugs. Several studies highlighted the usefulness of PDE-based drug screening and their predictive value or association with clinical responses, confirming the usefulness of this system to prospectively assess individual patient response (7,13,58).…”

Section: Discussionmentioning

confidence: 79%

3D tumor explant as a novel platform to investigate therapeutic pathways and predictive biomarkers in cancer patients

Rodolfo

Huber²,

Cossa³

et al. 2022

Front. Immunol.

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Immunotherapy with immune checkpoint inhibitors can induce durable clinical responses in different human malignancies but the number of responding patients remains globally modest. The limited therapeutic efficacy of ICI depends on multiple factors, among which the immune suppressive features of the tumor microenvironment play a key role. For this reason, experimental models that enable dissection of the immune-hostile tumor milieu components are required to unravel how to overcome resistance and obtain full-fledged anti-tumor immunity. Recent evidence supports the usefulness of 3D ex vivo systems in retaining features of tumor microenvironment to elucidate molecular and immunologic mechanisms of response and resistance to immune checkpoint blockade. In this perspective article we discuss the recent advances in patient-derived 3D tumor models and their potential in support of treatment decision making in clinical setting. We will also share our experience with dynamic bioreactor tumor explant culture of samples from melanoma and sarcoma patients as a reliable and promising platform to unravel immune responses to immune checkpoint inhibitors.

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Section: Discussionmentioning

confidence: 79%

3D tumor explant as a novel platform to investigate therapeutic pathways and predictive biomarkers in cancer patients

Rodolfo

Huber²,

Cossa³

et al. 2022

Front. Immunol.

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“…Drug resistance has always been a major obstacle in treatment of lung cancer (Shanker et al, 2010;Lim and Ma, 2019), and previously introduced models do not fully show the complexity of the tumour microenvironment. Organ-on-a-chip is able to simulate the in vivo tumour biology environment effectively and therefore has received increasing attention from scholars and inspired them to conduct indepth research (Nawroth et al, 2019;Guzzeloni et al, 2022). The LOC model allows for studying drug resistance in the context of the lung microenvironment, including effects of factors such as fluid flow, oxygen concentration, and cell-cell interactions.…”

Section: Progress In Loc In Lung Cancermentioning

confidence: 99%

Progress and application of lung-on-a-chip for lung cancer

Li,

Bo,

Wang

et al. 2024

Front. Bioeng. Biotechnol.

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Lung cancer is a malignant tumour with the highest incidence and mortality worldwide. Clinically effective therapy strategies are underutilized owing to the lack of efficient models for evaluating drug response. One of the main reasons for failure of anticancer drug therapy is development of drug resistance. Anticancer drugs face severe challenges such as poor biodistribution, restricted solubility, inadequate absorption, and drug accumulation. In recent years, “organ-on-a-chip” platforms, which can directly regulate the microenvironment of biomechanics, biochemistry and pathophysiology, have been developed rapidly and have shown great potential in clinical drug research. Lung-on-a-chip (LOC) is a new 3D model of bionic lungs with physiological functions created by micromachining technology on microfluidic chips. This approach may be able to partially replace animal and 2D cell culture models. To overcome drug resistance, LOC realizes personalized prediction of drug response by simulating the lung-related microenvironment in vitro, significantly enhancing therapeutic effectiveness, bioavailability, and pharmacokinetics while minimizing side effects. In this review, we present an overview of recent advances in the preparation of LOC and contrast it with earlier in vitro models. Finally, we describe recent advances in LOC. The combination of this technology with nanomedicine will provide an accurate and reliable treatment for preclinical evaluation.

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“…However, research on living animals raises ethical issues addressed through the 3Rs framework (Replacement, Reduction, Refinement) to reduce animal use [28,29]. Moreover, animal models are expensive, time-consuming, and require resources [30,31]. According to the Food and Drug Administration (FDA) report in 2004, less than 8% of medicinal compounds entering Phase I trials reach the market [25], which might be because mouse models still need to reproduce the complexity of human physiology and metabolism fully.…”

Section: Cse Decreased Cell Viability In a 2d Culture Modelmentioning

confidence: 99%

Pro-Apoptotic Activity and Cell Cycle Arrest of Caulerpa sertularioides against SKLU-1 Cancer Cell in 2D and 3D Cultures

et al. 2023

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Cancer is a disease with the highest mortality and morbidity rate worldwide. First-line drugs induce several side effects that drastically reduce the quality of life of people with this disease. Finding molecules to prevent it or generate less aggressiveness or no side effects is significant to counteract this problem. Therefore, this work searched for bioactive compounds of marine macroalgae as an alternative treatment. An 80% ethanol extract of dried Caulerpa sertularioides (CSE) was analyzed by HPLS-MS to identify the chemical components. CSE was utilized through a comparative 2D versus 3D culture model. Cisplatin (Cis) was used as a standard drug. The effects on cell viability, apoptosis, cell cycle, and tumor invasion were evaluated. The IC50 of CSE for the 2D model was 80.28 μg/mL versus 530 μg/mL for the 3D model after 24 h of treatment exposure. These results confirmed that the 3D model is more resistant to treatments and complex than the 2D model. CSE generated a loss of mitochondrial membrane potential, induced apoptosis by extrinsic and intrinsic pathways, upregulated caspases-3 and -7, and significantly decreased tumor invasion of a 3D SKLU-1 lung adenocarcinoma cell line. CSE generates biochemical and morphological changes in the plasma membrane and causes cell cycle arrest at the S and G2/M phases. These findings conclude that C. sertularioides is a potential candidate for alternative treatment against lung cancer. This work reinforced the use of complex models for drug screening and suggested using CSE’s primary component, caulerpin, to determine its effect and mechanism of action on SKLU-1 in the future. A multi-approach with molecular and histological analysis and combination with first-line drugs must be included.

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3D Models as a Tool to Assess the Anti-Tumor Efficacy of Therapeutic Antibodies: Advantages and Limitations

Cited by 5 publications

References 117 publications

3D tumor explant as a novel platform to investigate therapeutic pathways and predictive biomarkers in cancer patients

3D tumor explant as a novel platform to investigate therapeutic pathways and predictive biomarkers in cancer patients

Progress and application of lung-on-a-chip for lung cancer

Pro-Apoptotic Activity and Cell Cycle Arrest of Caulerpa sertularioides against SKLU-1 Cancer Cell in 2D and 3D Cultures

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