Immuno oncology
MIVOIMMUNO-OOC
The most predictive multi-organ-on-chip platform to test immuno-therapies and better understand mechanisms behind complex immune-tumor cells interplay.
Immunotherapies represent one of the current most promising challenges in cancer treatment.
To date, preclinical safety and efficacy assessments of immunotherapies are carried out through extensive in vitro cultures addressing the cellular and molecular basis of immune responses, in-vivo xenografts and genetically engineered animal models.
However, both approaches show limitations, and the success of immunotherapeutic approaches strictly depends on the development of highly reliable and predictive preclinical models.
IMMUNO-OOC is the most reliable and predictive platformfor immuno-oncology
FULLY HUMANIZED MICROENVIRONMENT
Immuno-oncology therapies testing dramatically need a
FULLY HUMANIZED MICROENVIRONMENT
due to the intricate interplay between the different immune cell subsets, tumour cells, and other cells within the Tumor MicroEnvironment (TME).
By adopting 3D in vitro/ex vivo human physiologically relevant cancer models cell yields can be improved, and the sample size is compatible with a wide variety of downstream standard analyses, maintaining a possible anisotropic cells behaviour.
SYSTEMIC CELL CULTURE BASED APPROACH
The introduction of FLUID FLOWS IN THE SYSTEMIC PLATFORM allows better mimicking the drug distribution and the dynamic tissue environment, affecting the molecule stability and the intra/extravasation of circulating cells (tumour cells or activated immune cells).
The combination of tumour models (either 2D or 3D) and fluid-dynamic cell culture makes relevant this in vitro pre-clinical system by reproducing the dynamic complex interactions between tumour cells and immune effectors transported in situ via systemic circulation.
IMMUNO-OOC is a unique organ-on-chip able to recapitulate the immune cells infiltration and activation against tumour cells in a 3D, fully humanized, and fluid-dynamic environment.
IMMUNO-OOC is based on the MIVO Technology, the preclinical in vitro platform compliant with the 3R approach (Reduce, Refine, Replace animal testing).
It supports spontaneous and tumour specific “extravasation” of immune cells toward the physically separated tumour niche, where a cytotoxic effect (tumour cell apoptosis) can be observed and quantified.
Fast, reproducible and more predictive quantification of the efficacy of novel immunomodulating agents through the analysis of tumour cell apoptosis can be carried out.
Tumor-specific immune cells (NK) extravasation (neg ctrl: cultre medium w/o supplements; pos ctrl: 3D matrix w/o tumor cells plus 30% serum; HTLA-230 cells: 3D matrix with standard 10% serum and embedded tumor cells)
Induction of apoptosis in tumor cells, assessed through flow cytometry. Control: tumor cells 3D monoculture.
nk cells (green) and neuroblastoma cells (red) within the 3D matrix. nuclei (blu) in panel D
In immuno-oncology, it is crucial to monitor and quantify the changes that occur in the tumour microenvironment, such as soluble molecules, cell death or immune cell invasion and activation inducing tumour cells death, and it is also essential to observe the behaviour of circulating immune cells.
That’s why finding alternative models for immunotherapy research is one of the main challenges for boosting efficacy in oncology towards personalized therapies with better effects on pathological patients.
The IMMUNO-OOC serves as a valuable and highly predictive approach where you can faithfully recapitulate the human pathology and efficiently run immunotherapies testing and dose-response studies in a fully humanized and immunocompetent in vitro platform.
In a multi-organ configuration, it is also possible to evaluate the interaction between the tumour and the metastatic site inside different compartments, physically connected through the circulating fluid flows.
The flexibility of this approach carries the significant potential of better recapitulating a clinical scenario, paving the way to:
1) a personalized investigation of the specific migratory and infiltrative capacity of immune cells,
2) the analysis of the anti-tumour activity of both drug-based and cell-based therapies,
3) the investigation of tumour-immune cells cross-talk, often leading to the onset of resistant tumour variants.
Technical advantages of IMMUNO-OOCthe fully humanized organ-on-chip for immuno-oncology
IMMUNO-OOC is optically transparent and PDMS-free, avoiding any cell/molecule adherence issues
Physical separation of tumour and vascular niches with specific cells culture conditions and infiltration studies
In vivo like immune cells circulation under physiological fluid flow conditions for more predictive outcomes
Constant monitoring and media sampling is possible anytime both in the tumour niche and the circulating cells compartment.
Easy recovery of circulating cells and tumour tissue for further investigations such as molecular, cytofluorimetric, confocal or optical analysis.
Compatibility with 3D tumour models like organoids or patient-derived biopsie, for more personalized therapies
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