Xenograft Models

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

Xenografts models of cancer involve the transplantation of human cancer cell line (CDX) or patient deprived tumors (PDX) into an immunodeficient or humanized mouse. PDX and CDX models are used to create an environment that allows for the natural growth of human cancer, its monitoring, and corresponding treatment evaluations of the original human cancer type. Many xenograft models have been successfully established for breast, prostate, colorectal, lung, and many other cancers because there are distinctive advantages when using xenografts. PDX models allow for the propagation and expansion of patient tumors without significant genetic transformation of tumor cells over multiple murine generations. Within PDX models, patient tumor samples grow in physiologically-relevant tumor microenvironments that mimic the oxygen, nutrient, and hormone levels that are found in the patient’s primary tumor site. Furthermore, implanted tumor tissue maintains the genetic and epigenetic abnormalities found in the patient. As a result, numerous studies have found that PDX models exhibit similar response to anti-cancer agents as seen in the actual patient who provided the tumor sample.

Examples of human cell lines that Melior uses include:

  • Breast – MCF7 and MCF7-Luc2 Cells
  • Colorectal – HCT-15 Cells
  • Hepatic – HepG2 Cells
  • Prostate – LNCap Cells

Chemotherapy Validation of HepG2 Subcutaneous Xenograft Model 5 x105 HepG2 human liver cancer cells were subcutaneously injected into the rear flank of athymic nude mice (Nu/J). Once mean tumor size reached 100-150mm3 (14 days after inoculation), mice were randomized into groups and treated with vehicle or paclitaxel (20 mg/kg) beginning on Day 0. Tumor growth volume was monitored twice / week using calipers until average control group tumors reached ~ 1,200 mm3 (Day 24). (Data area mean ± SEM; n=6 vehicle, n=5 paclitaxel)

Compared to syngeneic tumor models xenograph tumor models are not appropriate for anticancer agents targeting the immune system such as checkpoint inhibitors (e.g anti-CTLA4, anti-PD-1, anti-PD-L1).  Rather the xenograph models are suited for agents that directly modulate tumor cell growth such as cell cycle inhibitors and other traditional chemotherapeutic agents.

Our xenograft tumor models are ideal for evaluating novel human cancer cell target agents and combination therapies.