PDX Models

Discover how Melior’s unique phenotypic screening platforms can uncover the untapped value of your candidate therapeutic

Patient-derived xenograft (PDX) models are created by implanting fresh human tumor tissue directly into immunocompromised mice, as opposed to cell line-derived xenograft (CDX) models, which originate from established human cancer cell lines that have been passaged in culture for many generations before being implanted into mice. PDX models allow for tumors to grow in a microenvironment that more closely mimics the human tumor microenvironment, including the presence of stromal cells and extracellular matrix components.

While both forms of xenograft models utilize human cells in immunocompromised mice, PDX models are considered more clinically relevant than CDX models because they preserve the heterogeneity and genetic complexity of the original tumor and can better predict patient response to treatment.  While CDX models are easier and faster to create than PDX models, they do not capture the full complexity of the tumor microenvironment, and their responses to treatment may not accurately reflect what is seen in patients.  PDX models contain all of the genetic and epigenetic changes that were present in the patient’s tumor, while CDX models only contain the genetic changes that were present in the cancer cell line.  In addition, PDX models are more heterogeneous than CDX models because contain a variety of different cell types, while CDX models are typically composed of a single cell type.  As a result, PDX models response to a given treatment may more faithfully recapitulate the response of the patient’s original tumor.

While PDX models may be run in immunocompromised animals and therefore are not suitable for studying immune therapies such as CAR-T or checkpoint inhibitors (exception being humanized mouse host), their faithful recapitulation of the human tumor microenvironment and genetic heterogeneity make them particularly well-suited for evaluating targeted therapies such as monoclonal antibodies or combination therapies.

Chemotherapy validation in human colon cancer PDX 121-R subcutaneous model. This tumor was excised from a colon adenocarcinoma of a 62-year-old white male in 2017 (P0). The tumor grade /stage was designated as: pT3 pN1b Mx. The tumor tissue was subsequently passaged 3x over approximately 3 months in NSG mice (P3). For this study the mice were subcutaneously implanted with a small piece of P3 121-R tumor with Matrigel into the rear flank of NSG mice with 11G trocar. Once the tumor size reached ~150mm3 (Day 7), the mice were randomized into vehicle control group (treated with normal saline) and paclitaxel group (20 mg/kg, IP twice/week). Tumor volume was monitored twice per week using calipers (A). At the end of the study (Day 45), animals were sacrificed, tumors excised and weighted (B, C). Data are mean ± SEM; n=6 /group; ** p<0.01 by Student’s t-test.

If you have access to clinical samples from which you want to initiate a PDX study Melior is able to, with short lead times, and flexibility for bespoke study designs, accommodate most client needs.

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