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Patient-Derived Cells (PDC) for Drug Development

Mediford Corporation provides various contract services using clinical isolates (PDC: Patient-Derived Cell) established at the National Cancer Center in Japan.

About PDC

What is PDC?

PDCs established by the National Cancer Center (Dr. Hiroki Sasaki) are cell lines from cells contained in ascites fluid of patients with ascites due to peritoneal dissemination of gastric or pancreatic cancer. They are stored at low passages and maintain a heterogeneous cell population including tumor cells. They are more similar to the cancer cells in the patient's cancer tissue than cultured cell lines, making them useful for evaluating the efficacy of anticancer drugs.

What is PDC?

Features of PDC

  • Cancer cells collected from a patient are passaged three or five times and transformed into a cell line.
  • Cells up to 100 passages are used.
  • Whole exome analysis and microarray (Affymetrix U133 Plus 2.0) are performed.
  • In vitro (2D culture) drug efficacy evaluation is conducted in collaboration with the National Cancer Center (using cisplatin, docetaxel, gemcitabine, etc.).

PDC derived from ascites fluid of gastric cancer patients: 45 cell lines

Cell lines of diffuse type gastric cancer with poor prognosis as represented by scirrhous gastric cancer

References:
Tanaka Y, Chiwaki F, .., Sasaki H, Mano H. Multi-omic profiling of peritoneal metastasis in gastric cancer identifies molecular subtypes and therapeutic vulnerabilities. Nat. Cancer. 2021 Aug. doi.org/10.1038/s43018-021-00240-6. Komatsu M, .., Sasaki H. ARHGAP–RhoA signaling provokes homotypic adhesion-triggered cell death of metastasized diffuse-type gastric cancer. Oncogene. 2022 Sept 20. doi.org/10.1038/s41388-022-02469-6.

PDC derived from ascites fluid of pancreatic cancer patients: 38 cell lines

36 cell lines of adenocarcinoma, 1 cell line of squamous cell carcinoma, 1 cell line of adenosquamous carcinoma

Reference:
Sasaki H. (ed.), Practical Guide for Cancer Research Using Patient-Derived Cancer Models, Yodosha, 2019.

Commissioned business

In Vitro Study Using PDC (2D culture)

We evaluate the anti-tumor effect in vitro using gastric cancer PDC and pancreatic cancer PDC by 2D culture, which has been conducted for some time.

Example

We evaluated the effects of docetaxel, cisplatin, and gemcitabine on 23 pancreatic cancer PDC cell lines.

①Effects of docetaxel on PDC23 pancreatic cancer and cultured pancreatic cancer cell lines
②Effect of cisplatin on PDC23 pancreatic cancer and cultured pancreatic cancer cell line
③Effect of gemcitabine on PDC23 pancreatic cancer and cultured pancreatic cancer cell lines

Conclusion

In ① to ③, differences were observed in the sensitivity of pancreatic cancer PDC23 cell line to docetaxel, cisplatin, and gemcitabine, indicating that the pancreatic cancer PDC23 cell line is useful as a panel test.

For details of the experiment, click here.

In Vitro Study Using PDC (3D culture)

We have developed a 3D culture method (international patent pending (WO2018/169007), partially registered).
Using this technology, we can culture PDC of pancreatic cancer and gastric cancer in 3D and evaluate the anti-tumor effect of anti-cancer drugs.

Example

Two types of gastric cancer PDC (NSC-11C, NSC-22C) were cultured in 3D and the effects of anti-cancer drugs (docetaxel and cisplatin) were evaluated.

Effect of docetaxel

mean ± standard deviations (n=3)

Effect of cisplatin

mean ± standard deviations (n=3)

Concentrations of anticancer drugs near IC50 vs. control spheroid size
control docetaxel 62.5 pM *1 cisplatin 1.56 µM *2
NSC-11C
NSC-22C

Scale bar: 500 μm

*1: Docetaxel concentration near IC50 in 2D culture method
*2: Cisplatin concentration near IC50 in 3D culture method

Conclusion

3D culture shows a difference in the effect of anticancer drugs on gastric cancer PDC.

In Vivo Study Using PDC

We evaluate the anti-tumor effects of various drugs on the growing tumors in vivo by implanting gastric cancer PDCs or pancreatic cancer PDCs subcutaneously in immunodeficient mice.

Example①

Anticancer effect of cisplatin, docetaxel, and capecitabine on two types of gastric cancer PDC (NSC-10C, NSC-14C) was confirmed.

Pathological images of tumors created by subcutaneously transplanting gastric cancer PDCs (NSC-10C, NSC-14C) into immunodeficient mice
HE CXCR4 CD44
NSC-10C
NSC-14C

Scale bar: 200 μm

CXCR4：Molecule that mediate cancer metastasis
CD44：One of the major cell surface markers of cancer stem cells

Results of anticancer study
NSC-10C
NSC-14C
Conclusion

Each PDC has different sensitivity to anticancer drugs, and PDC as well as PDX can be used as avatars of patients.

Example②

We evaluated the anticancer effect of gemcitabine on two types of pancreatic cancer PDC (NPC-7C, NPC-20C).

Pathological images of tumors created by subcutaneously transplanting pancreatic cancer PDCs (NPC-7C, NPC20-C) into immunodeficient mice.
HE CXCR4 CD44
NPC-7C
NPC-20C

Scale bar: 200 μm

CXCR4：Molecule that mediate cancer metastasis
CD44：One of the major cell surface markers of cancer stem cells

Results of anticancer study
NPC-7C
NPC-20C
Conclusion

Each PDC has different sensitivity to anticancer drugs, and PDC as well as PDX can be used as patient avatars.

Test Period

Standard test period

In vitro (2D culture method)
About 4 months
In vitro (3D culture method)
About 4 months
in vivo
About 6 months

Advanced Solutions

Patient-Derived Xenografts (PDX) for Drug Development
Patient-Derived Xenografts (PDX) for Drug Development

Mediford Corporation offers a variety of contract services from establishment and banking of PDX-derived cell lines to conducting pharmacological studies at the GLP-certified facilities of Kumamoto Laboratories. The PDX models are more predictive of clinical outcomes than conventional "cancer cell lines" and will be useful for your research and development purposes.