Skip to Content
Patient-Derived Models Repository (PDMR)
Last Updated: 03/08/17

NCI PDMR Models Overview

Diagram of the PDMR Model Generation Workflow

Overview

The PDMRs primary source of patient material are two NCI-sponsored protocols: NCI Tissue Procurement Protocol (clincialtrials.gov: NCT00900198) and CIRB Tissue Procurement Protocol 9846. In addition to fresh tissue specimens, we have also obtained viably cryopreserved patient tumor tissue, rapid autopsy material, and previously-derived PDXs from outside groups. All such specimens have been collected under IRB-approved protocols and released through MTAs to allow use and distribution with the PDMR.

The goal is to have at least 1000 PDX models available in the PDMR. In the future, early-passage mixed tumor cultures as well as cancer-associated fibroblast cultures will be released through the PDMR for many of the same originating patients. We continue to seek external site (profit and non-profit) contributors to provide previously-derived models or patient material to the PDMR for model generation and release to the research community. All models received by the PDMR go through the same QC procedures that are applied to internally-derived models.

Quality Control

The PDMR places stringent QC criteria on models. The PDMR expands its models by fragment engraftment to maintain as much tumor heterogeneity as possible. In addition, the distribution lots are early passage — generally P1-P4. Because of this, variations in histology and in low allele frequency genetic variants can be observed in lineages within a model. These same type of variations can be expected in PDX models expanded by the recipients of distributed fragments from the repository. While PDX models generally demonstrate a high degree of stability once they reach P3-5, the PDMR has observed some models that continue to evolve; this caveat should be considered by any investigator requesting models for their research aims.

Data associated with PDMs from individual patients and specimens will only be displayed in the public PDMR database once the model has (1) reached at least passage 1, (2) been proven to be of human origin, (3) been confirmed by histopathology to match the patient diagnosis or pathology or provided patient material, (4) completed IDEXX human pathogen assessment, (5) been successfully regrown from cryopreserved material, and (6) data are available from at least one PDX for the NCI Cancer Gene Panel, whole exome sequencing, and RNASeq.

PDMR Definitions

Patient Derived Models (PDM): Preclinical models originating from fresh patient malignant tumor or circulating tumor cells (CTCs) from blood specimens.

Patient-Derived Xenograft (PDX): A tumor model generated by implantation of fresh human tissue (tumor, enriched CTCs) into immunodeficient mice. The PDMR host mouse model used is NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG).

  • Originator: Original patient material used for model generation
  • Passage 0 (P0): First mouse passage implanted with the original human specimen

In development: Patient-Derived Cell Cultures (PDC) are low passage, non-clonal cell cultures generated by growth of human tissue (patient tumor material, enriched CTCs, PDX tumors) in in vitro culture. The optimal growth conditions for individual PDCs will be provided with the sample.

  • Patient-Derived Mixed Cell Culture: 99.9% human tumor culture, non-clonal (multiple cell types or non-cloned lineages), 99.9% fibroblast free (FACs analysis). These cultures have been grown for at least 20 passages from the distribution lot and no out-growth of fibroblasts has been observed. The distribution lot has also been subcutaneously implanted into NSG mice to test for tumorigenicity. These cultures may or may not be able to form spheroids in a fully-defined, serum- and feeder-free medium or in soft agar.
  • Fibroblast human cell culture: 99.9% human fibroblast culture and 99.9% human tumor cell free (FACs analysis). These cultures have been proven to be non-tumorigenic following subcutaneous implantation into NSG mice and have been characterized as fibroblasts by at least one of the following methods: immunohistochemistry, qRT-PCR, or FACs.