Evaluation of Cell-able OncologyTM spheroid culture systemfor culturing patient derived primary tumor cells
Kesavan Nair Praveen, Nicole Streiner, Martin Vo, Kenna Anderes, Koichi Yokota, Takeshi Ikeya
Molecular Response LLC, 10865 Road to the Cure, San Diego, CA 92121 USA, Transparent Inc, 4-2-1 Wakahagi, Inzai, Chiba, 270-1609 Japan

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Patient Derived Primary Tumor Cells

Cell-able OncologyTM Spheroid culture system

High Content Imaging in Patient Derived Primary Tumor Cells in 3D environmentA)B)
3D

Molecular Response PTC Bank
Beyond Banked Tumor Tissue
Tumor Biopsy
or resection

Single cellsuspension

Cryopreserved“Live Biologically Intact
Samples”

On ECM

Cryopreserved
Samples

Cell-able

Creation of companion Biobank: Matched DNA, RNA and proteinfrom cryopreserved cells
DNA: mutations, copy number, translocation
RNA: gene expression, splice variation
Protein: antigen detection, size variation

Photolithographic process to fabricate 3-dimensional cellstructure: Chemical surface modification using photosensitive &non cell-attaching polymer on the cell culture plate.

Ex vivo studies on Tumor cells: 2D vs 3D: (A) Comparison of 3D and 2D assays: Action and potency of cancer drugs dependon the culture conditions of tumor cells ex vivo. (B) Patient-derived tumor cells can be grown as tumor spheroids using different
methods. Blue: DAPI, Green: Cytokeratin, Red: EdU

Novel 3D culture system for Oncology Drug Discovery

Cell-able OncologyTM plates as a tool for drug response studies

High-Content Imaging of Tumor Spheroids in Cell-able OncologyTM PlatesPatient-derived tumor cells and tumor cell lines grow intospheroids.
Compatible with relevant endpoints used in drug discovery.
Easy to handle and image compared with 3D ECM culture.
Similar drug sensitivity to 3D ECM culture.
Applicable to use in basic through clinical research in oncology.

Patient-derived tumor samples from bio-bank

HCC PTC

H&N PTC

MEL PTC

Cell-able

2D

Cell-able Spheroid Culture System: A Powerful Tool for Oncology Drug Discovery Programs
Cancer Cells Grow as Spheroids on Cell-able OncologyTM Plates

In ECM

CBDCA 1 M

CBDCA 10 M

CBDCA 100 M

mTOR 10 nM

mTOR 100 nM

mTOR 1000 nM

BRE PTC
UTC

Integrated Approaches to Discovery and Clinical Utility
PI3K 0.1 M

PI3K 1 M

PI3K 10 M
PreclinicalFresh (Non-cryopreserved)Tumor samples

Proprietary
Tumor Bank
Cell-able OncologyTM

Papanicolaou

OVA: Serous

Cytokeratin

EpCAM

OVA: Clear Cell

Phase I

Create Multiple Hypotheses

Phase IIa/b
Test Multiple Hypotheses

ClinicalReference Lab(CLIA/CAP)

Phase III
Test Single Hypothesis

On Market
Launch Test

Hand-off to IVD/Commercialization
Partnerfor PMA

Cytokeratin

Endometrial

Cell-able OncologyTM plates as a novel 3D spheroid culture: Patient-derived tumor cells(freshly collected as well as cryopreserved) grow as 3D spheroids on Cell-able OncologyTM
plates. Tumor cell lines also form spheroids on Cell-able OncologyTM plates.

Use of Cell-able OncologyTM plates for ex vivo treatment studies: Patient-derived tumorcells (freshly collected) were grown as 3D spheroids on Cell-able OncologyTM plates and weretreated with oncology drug candidates. Change in the proliferation were visualized by EdU
uptake and quantified using WST-8 Assay. Blue: DAPI, Green: EdU

Combining Cell-able OncologyTM plates with High-Content Imaging Platform: Patient-derived tumorcells (cryopreserved) were grown as 3D spheroids on Cell-able OncologyTM plates and were treated withoncology drug candidates. Change in the proliferation were visualized by EdU uptake, apoptosis by Caspase 3/7
assay. Imaging and analysis were performed using ImageXpress Micro and MetaXpress (Molecular Devices,Sunnyvale, CA). Blue: DAPI, Red: EdU

Copyright 2011-2012 Molecular Response, LLC. All Rights Reserved.

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