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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.

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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% of 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.  

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 to find out more about the characteristics of this model.

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.

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