zPREDICTA®, a Unique 3D Cell Culture Technology Solution

3D Cell Culture

A patient’s response to anticancer therapeutics depends on the specific architecture and cellular composition of the tumor microenvironment. Therefore, 3D cell culture models that mimic actual human tissue are an essential preclinical tool to understand how anticancer drug candidates might behave in a patient. Additionally, the development of 3D systems supports our commitment to apply techniques that decrease the number of animals used in our research.

Reduce risk and move candidates forward confidently with 3D cell culture technology

3D cell culture technology overcomes the limitations of 2D (monolayer) cell culture assays by taking into account the effect of the tumor microenvironment on tumor progression and treatment resistance. Even though potential anticancer drugs show high efficacy during preclinical testing using 2D in vitro models, about 95%¹of these fail clinical trials due to lack of efficacy and high toxicity. This is because the 2D cell culture assays do not closely mimic the physiological conditions where tumors grow and proliferate, therefore they do not provide a true prediction of the clinical response. The use of tumor-specific 3D culture models that mimic the human tissue environment, including the in vivo cell–cell/cell–extracellular matrix (ECM) interactions and phenomena such as hypoxia, necrosis, angiogenesis and cell adhesion, is, therefore, essential. This enables you to test anticancer drugs in a system that more accurately replicates that of the human body.

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Reconstructed Plate-Based 3D Screening Assays That Predict In Vivo Response

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Our capabilities: we are leveraging 3D cell culture technology to enhance your preclinical research

zPREDICTA’s patient-derived, organ-specific, tumor-specific 3D culture platform is essential in obtaining accurate clinical response data

Our mission is to reduce the failure rate of candidate anticancer drugs in clinical trials by providing our clients with access to advanced tumor-specific 3D in vitro models. We continue to invest in innovative technology that improves oncology drug discovery and research. zPREDICTA 3D in vitro models provide us with a new tool that produces more reliable outcomes for early evaluation of responses to oncology and immuno-oncology therapies.

These unique cell culture models provide 3D reconstruction of human tissues, accurately representing each disease state and providing an environment in which you can more realistically simulate the drug responses you would expect to obtain in vivo. This comprehensive 3D culture platform integrates organ-specific cellular and extracellular elements to maintain the critical interactions between a tumor and its surroundings. This technology allows you to eliminate ineffective compounds early in the drug development process and move forward with promising candidates.

What can our use of the zPREDICTA organ-specific 3D culture models offer you?

Results obtained from zPREDICTA models display a high level of correlation with clinical response. This means it can help reliably predict the potential clinical outcomes of your potential therapeutic agent in a range of cancer models and tissues. Features of the zPREDICTA model include:

3D spheroidal models of cancer cell lines derived from solid tumors and hematological malignancies (Table 1)
Patient-derived models from primary tumors grown in a 3D ECM for indications such as acute myeloid leukemia and multiple myeloma
Co-culture/multi-compartment models: for example, the reconstructed metastasis (r-Met) multi-compartment model is the only available model that provides access to the metastatic cell population for target discovery and drug testing
Fully customizable to the tumor and tissue of interest: it is compatible with multiple cell types, drug classes (including small molecules, antibodies, antibody-drug conjugates (ADC), immunomodulatory agents, CAR-T cells, etc), and downstream analysis methods

Table 1: 3D models systems available

MODEL	TUMOROIDS Human \| Mouse		CO-CULTURE* (w/ tumor cell line)	PRIMARY CELLS / PRIMARY CO-CULTURE	MODEL TYPE	SPECIES
r-Bone (bone marrow)	NCI-H929 RPMI-8226 U266 KMS-12 XG-6	J558(in progress) 5TGM1 (in progress)	MSC BMMC PBMC T cells Purified immune cells	Multiple myeloma BMMC AML BMMC Healthy BMMC	Tumor Bone marrow toxicity Solid tumor metastasis	Human Mouse
r-Breast	BT-474 CAL51 MCF10 progression MCF7 MDA-MB-231 SK-BR3 T47D ZR75	4T1 EMT6 E0071 PyMT	Fibroblasts CAFs MSC PBMC Purified immune cells (T, B, dendritic cells)	HMEC Triple Negative (in progress) ER+/PR+ (in progress)	Tumor Metastasis	Human Mouse
r-Lung	A549 NCI-H460 HCC827			NSCLC (in progress)	Tumor Metastasis	Human
r-Stomach	MKN-74 AGS				Tumor	Human
TUBE formation assay				HUVEC Endothelial cells	Endothelial tube formation	Human Mouse
r-Liver (in development)	TBD	TBD		Hepatocytes (in progress) Stellate cells	Tumor Drug metabolism and toxicity	Human Rat Mouse
r-Pancreas (in development)	MiaPaca2 Panc1				Tumor	Human

*BMMC, bone marrow mononuclear cells; CAFs, cancer-associated fibroblasts; MSC, mesenchymal stem cells; PBMC, peripheral blood mononuclear cells

What testing can we perform with 3D cell culture technology?

Efficacy screening of anticancer compounds and drug combinations (both small molecules and biologics)
Evaluate a wide range of oncology immunotherapies, such as antibody–drug conjugates (ADC), bi/tri-specifics, CAR-T cells
Determine mechanism(s) of action and immune-regulation
Determine mechanisms of drug resistance
Rescue of failed drug candidates
Assessment of off-target toxicity
Evaluate remodeling of tumor microenvironment
Drug discovery in primary and metastatic tumors

Through our partnership with zPREDICTA, we aim to drive the adoption of 3D cell culture technology

As part of our focus to bring forward solutions to advance efficient development of oncology therapeutics, we have partnered with zPREDICTA to develop and commercialize tumor-specific 3D preclinical models based on their highly advanced technology. As an example, the reconstructed Bone (r-Bone) model is a plate-based, 3D culture assay that mimics the tumor microenvironment found in multiple myeloma, acute myelogenous leukemia and solid tumor metastasis. See our tech spotlight and watch our webinar to find out more about the characteristics of this model.

References:

Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov. 2004 Aug;3(8):711-5. doi: 10.1038/nrd1470. PMID: 1528673

To use zPREDICTA’s unique 3D cell culture platform for your preclinical oncology and immuno-oncology research, contact the scientists at Labcorp Drug Development’s Preclinical Oncology team.