Modeling human tumor-immune environments in vivo for the preclinical assessment of immunotherapies DOI Creative Commons
Bethany Bareham, Nikitas Georgakopoulos, Alba Matas‐Céspedes

et al.

Cancer Immunology Immunotherapy, Journal Year: 2021, Volume and Issue: 70(10), P. 2737 - 2750

Published: April 8, 2021

Abstract Despite the significant contributions of immunocompetent mouse models to development and assessment cancer immunotherapies, they inadequately represent genetic biological complexity corresponding human cancers. Immunocompromised mice reconstituted with a immune system (HIS) engrafted patient-derived tumor xenografts are promising novel preclinical model for study tumor-immune interactions. Whilst overcoming limitations models, HIS-tumor often rely on reconstitution allogeneic cells, making it difficult distinguish between anti-tumor alloantigen responses. Models that comprise autologous cells provide platform is more representative patient immune-tumor interaction. However, limited access tissues, short experimental windows, poor retention microenvironment infiltrating lymphocyte components major challenges affecting establishment application models. This review outlines existing murine immuno-oncology, highlights innovations can be applied improve feasibility efficacy

Language: Английский

Organoid and Spheroid Tumor Models: Techniques and Applications DOI Open Access

Sreenivasulu Gunti,

Austin T.K. Hoke, Kenny Vu

et al.

Cancers, Journal Year: 2021, Volume and Issue: 13(4), P. 874 - 874

Published: Feb. 19, 2021

Techniques to develop three-dimensional cell culture models are rapidly expanding bridge the gap between conventional and animal models. Organoid spheroid cultures have distinct overlapping purposes differ in cellular sources protocol for establishment. Spheroids of lower complexity structurally but simple popular drug screening. Organoids histologically genetically resemble original tumor from which they were derived. Ease generation, ability long-term cryopreservation make organoids suitable a wide range applications. Organoids-on-chip combine organoid methods with powerful designing fabrication micro-chip technology. Organoid-chip can emulate dynamic microenvironment pathophysiology as well tissue–tissue interactions. In this review, we outline different techniques establish them. We also discuss recent advances applications an emphasis on modeling, screening, personalized medicine immunotherapy.

Language: Английский

Citations

317

Nanomedicine in cancer therapy DOI Creative Commons

Dahua Fan,

Yongkai Cao,

Meiqun Cao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 7, 2023

Cancer remains a highly lethal disease in the world. Currently, either conventional cancer therapies or modern immunotherapies are non-tumor-targeted therapeutic approaches that cannot accurately distinguish malignant cells from healthy ones, giving rise to multiple undesired side effects. Recent advances nanotechnology, accompanied by our growing understanding of biology and nano-bio interactions, have led development series nanocarriers, which aim improve efficacy while reducing off-target toxicity encapsulated anticancer agents through tumor tissue-, cell-, organelle-specific targeting. However, vast majority nanocarriers do not possess hierarchical targeting capability, their indices often compromised poor accumulation, inefficient cellular internalization, inaccurate subcellular localization. This Review outlines current prospective strategies design organelle-targeted nanomedicines, highlights latest progress technologies can dynamically integrate these three different stages static maximize outcomes. Finally, we briefly discuss challenges future opportunities for clinical translation nanomedicines.

Language: Английский

Citations

287

Microengineered perfusable 3D-bioprinted glioblastoma model for in vivo mimicry of tumor microenvironment DOI Creative Commons
Lena Neufeld, Eilam Yeini, Noa Reisman

et al.

Science Advances, Journal Year: 2021, Volume and Issue: 7(34)

Published: Aug. 18, 2021

A perfusable vascularized 3D-bioprinted cancer model with stromal cells can be used for personalized therapy and target discovery.

Language: Английский

Citations

138

A role for microfluidic systems in precision medicine DOI Creative Commons
José M. Ayuso, Marı́a Virumbrales-Muñoz, Joshua M. Lang

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: June 2, 2022

Precision oncology continues to challenge the "one-size-fits-all" dogma. Under precision banner, cancer patients are screened for molecular tumor alterations that predict treatment response, ideally leading optimal treatments. Functional assays directly evaluate efficacy on patient's cells offer an alternative and complementary tool improve accuracy of oncology. Unfortunately, traditional Petri dish-based overlook much complexity, limiting their potential as predictive functional biomarkers. Here, we review past applications microfluidic systems medicine discuss present future role predictors.

Language: Английский

Citations

130

Applications of Microfluidics and Organ-on-a-Chip in Cancer Research DOI Creative Commons
Sagar Regmi, Chetan Poudel, Rameshwar Adhikari

et al.

Biosensors, Journal Year: 2022, Volume and Issue: 12(7), P. 459 - 459

Published: June 27, 2022

Taking the life of nearly 10 million people annually, cancer has become one major causes mortality worldwide and a hot topic for researchers to find innovative approaches demystify disease drug development. Having its root lying in microelectronics, microfluidics seems hold great potential explore our limited knowledge field oncology. It offers numerous advantages such as low sample volume, minimal cost, parallelization, portability been advanced molecular biology chemical synthesis. The platform proved be valuable research, especially diagnostics prognosis purposes successfully employed recent years. Organ-on-a-chip, biomimetic microfluidic platform, simulating complexity human organ, emerged breakthrough research it provides dynamic simulate tumor growth progression chip. This paper aims at giving an overview organ-on-a-chip technology incorporating their historical development, physics fluid flow application current applications have copiously discussed integrating areas isolation CTCs, studying cell phenotype well metastasis, replicating TME technology's significance limitations are also addressed, readers comprehensive picture ability advance

Language: Английский

Citations

74

Bioengineered 3D models of human pancreatic cancer recapitulate in vivo tumour biology DOI Creative Commons
David Osuna de la Peña,

Sara Trabulo,

Estelle Collin

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 24, 2021

Patient-derived in vivo models of human cancer have become a reality, yet their turnaround time is inadequate for clinical applications. Therefore, tailored ex that faithfully recapitulate tumour biology are urgently needed. These may especially benefit the management pancreatic ductal adenocarcinoma (PDAC), where therapy failure has been ascribed to its high stem cell (CSC) content and density stromal cells extracellular matrix (ECM). To date, these features only partially reproduced using organoid sphere cultures. We now developed more comprehensive highly tuneable model PDAC based on 3D co-assembly peptide amphiphiles (PAs) with custom ECM components (PA-ECM). cultures maintain patient-specific transcriptional profiles exhibit CSC functionality, including strong tumourigenicity. User-defined modification system enables control over niche-dependent phenotypes such as epithelial-to-mesenchymal transition deposition. Indeed, proteomic analysis reveals improved matrisome recapitulation compared organoids. Most importantly, drug responses better self-assembled than other models. findings support use self-assembling platforms research pave way future precision medicine approaches.

Language: Английский

Citations

93

A microfluidic platform for cultivating ovarian cancer spheroids and testing their responses to chemotherapies DOI Creative Commons
Neda Dadgar, Alan M. Gonzalez‐Suarez, Pouria Fattahi

et al.

Microsystems & Nanoengineering, Journal Year: 2020, Volume and Issue: 6(1)

Published: Oct. 19, 2020

Abstract There is increasing interest in utilizing vitro cultures as patient avatars to develop personalized treatment for cancer. Typical utilize Matrigel-coated plates and media promote the proliferation of cancer cells spheroids or tumor explants. However, standard culture conditions operate large volumes require a high concentration initiate this process. Other limitations include variability ability successfully establish stable line inconsistency dimensions these microcancers vivo drug response measurements. This paper explored utility microfluidics cultivation cell spheroids. Six patient-derived xenograft (PDX) tumors high-grade serous ovarian were used source material demonstrate that viability epithelial marker expression microfluidic was superior Matrigel volume 3D cultures. To further potential miniaturization multiplexing, we fabricated multichamber devices with integrated microvalves enable serial seeding several chambers followed by parallel testing concentrations. These valve-enabled permitted formation seven concentrations few 100,000 per device. Overall, feasibility maintaining difficul-to-culture primary drugs platform may be ideal therapy when limited, such following acquisition biopsy specimens obtained fine-needle aspiration.

Language: Английский

Citations

83

Tumor-on-chip modeling of organ-specific cancer and metastasis DOI Creative Commons
Nuala Del Piccolo, Venktesh S. Shirure, Ye Bi

et al.

Advanced Drug Delivery Reviews, Journal Year: 2021, Volume and Issue: 175, P. 113798 - 113798

Published: May 18, 2021

Every year, cancer claims millions of lives around the globe. Unfortunately, model systems that accurately mimic human oncology – a requirement for development more effective therapies these patients remain elusive. Tumor is an organ-specific process involves modification existing tissue features, recruitment other cell types, and eventual metastasis to distant organs. Recently, engineered microfluidic devices have emerged as powerful in vitro tool physiology pathology with organ-specificity. These organ-on-chip platforms consist cells cultured 3D hydrogels offer precise control over geometry, biological components, physiochemical properties. Here, we review progress towards models primary metastatic tumor microenvironments. Despite field's infancy, tumor-on-chip enabled discoveries about immunobiology response therapy. Future work should focus on autologous or multi-organ inclusion immune system.

Language: Английский

Citations

82

Advancements in 3D Cell Culture Systems for Personalizing Anti-Cancer Therapies DOI Creative Commons
Andrew M. K. Law, Laura Rodríguez de la Fuente,

Thomas J. Grundy

et al.

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: Nov. 30, 2021

Over 90% of potential anti-cancer drug candidates results in translational failures clinical trials. The main reason for this failure can be attributed to the non-accurate pre-clinical models that are being currently used development and personalised therapies. To ensure assessment efficacy their mechanism action have translatability, complexity tumor microenvironment needs properly modelled. 3D culture emerging as a powerful research tool recapitulates vivo characteristics. Technological advancements field show promising application improving discovery, validation, precision medicine. In review, we discuss significance its impact on therapy success, current developments culture, opportunities vitro technologies provide improve cancer therapeutics.

Language: Английский

Citations

67

In Vitro 3D Cultures to Model the Tumor Microenvironment DOI Open Access
Fabrizio Fontana, Monica Marzagalli, Michele Sommariva

et al.

Cancers, Journal Year: 2021, Volume and Issue: 13(12), P. 2970 - 2970

Published: June 13, 2021

It is now well established that the tumor microenvironment plays a key role in determining cancer growth, metastasis and drug resistance. Thus, it fundamental to understand how cells interact communicate with their stroma this crosstalk regulates disease initiation progression. In setting, 3D cell cultures have gained lot of interest last two decades, due ability better recapitulate complexity therefore bridge gap between 2D monolayers animal models. Herein, we present an overview systems commonly used for studying tumor-stroma interactions, focus on recent advances modeling discovery testing.

Language: Английский

Citations

66