Patient-derived Xenografts of Hematological Malignancies: Model Systems for Drug Development and Tumor Biology Research

In recent years, there have been multiple efforts in the establishment and characterization of large collections of Patient-Derived Tumor Xenograft (PDX) models for cancer research. Although this model system was developed already in the late 1980´s, it has come into focus lately due to its predictivity for clinical outcome and utility in biomarker development. PDX models mainly retain the histological and genetic characteristics of the donor tumor and remain stable across passages. They preserve cell-autonomous heterogeneity thereby representing very well the molecular landscape of the corresponding disease. Since triple immune deficient mouse strains like NOD/Shi-scid/IL-2Rγ null (NOG) mice were made available to the scientific community; PDX of hematological malignancies could be established to a similar extend as their solid counterparts. Despite the incontrovertible advantages of PDX as preclinical models in drug development, pharma research faces a high failure rate combined with rising research and development costs of new drugs particularly in early clinical development. In view of success rates below 5% for innovative cancer drugs, improvements in model development are urgently needed.

Patient-Derived Tumor Xenograft (PDX) models for cancer research have come into focus lately due to their predictivity for clinical outcome and utility in biomarker development. As super immunodeficient strains such as the CIEA NOG mouse® became available, PDX of hematological malignancies could be established to a similar extent as their solid tumor counterparts. Within the last 2 years, Oncotest has developed 48 acute leukemia PDX models and started to develop a similar panel for different Non-Hodgkin Lymphomas.

Key learning points:

• How hematological patient-derived xenograft (PDX) models are established
• How more super immune deficient mouse models have advanced development of hematological PDX models
• Why hematological PDX models are more translational than cell line-derived models
• How hematological PDX models can be employed in drug discovery and development

Speakers

Julia Schueler, Department Head, In Vivo Tumor Biology, Oncotest GmbH

Julia Schueler received a DVM degree in 1997 and a PhD in veterinary medicine in 1999, both from the University of Berlin. She then did a postdoc in the lab of Thomas Böhm at the Max Planck Institute for Immunobiology. She joined Oncotest in 2002 as lab head for in vivo contract research. In 2005 she became lab head for in vivo R&D. Finally in 2011, she became the department head for in vivo tumor biology at Oncotest.

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Megan MacBride , Associate Director, Product Management, Taconic Biociences

Megan MacBride received an AB in Chemistry from Princeton University. She received a PhD in Chemistry from The Pennsylvania State University, where her doctoral research focused on drug discovery for nuclear receptors. She was a Senior Scientist at Indigo Biosciences, a contract research organization. In 2006, Dr. MacBride joined Taconic as a product manager. As part of the product management group, she has successfully launched many new transgenic animal products. In her current position of Associate Director, Product Management, she manages a large portion of Taconic’s animal model portfolio.

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