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PATh PDX/CDX & Surgical Facility

The Progressive Assessment of Therapeutics (PATh) PDX Facility was established to provide comprehensive services and facilities to further the development and characterization of patient-derived xenograft (PDX) cancer models. PDX models using the NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) immunodeficient mice provide the most clinically relevant tumor models, which faithfully recapitulate the original tumor histology, genetic profile, and response/resistance to therapy.

The advantages associated with PDX mouse models include:

  • Ability to more easily establish novel tumor lines (Human, Canine, etc...)
  • Ability to test drug sensitivity in an in vivo model
  • Simple subcutaneous engrafting technique
  • Improved predictability of treatment outcomes and prognosis
  • Potential applications in personalized precision medical treatments
  • Ease of access to the subcutaneous tumor for biopsy
  • Preserved tumor heterogeneity
  • Allows for effective chronological tumor size monitoring

The PATh program operates on a cost recovery model, which allows us to pass on significant savings to the end user (you), some of which include animal costs and MR imaging time. PATh services are available to all Cornell and Weill Cornell investigators, outside institutions, industry, and private organizations.

The Facility Infrastructure

Our facility has extensive infrastructure to provide our clients with a full array of services ranging from the delivery of NSG mice to helping design and run preclinical trials with MR imaging. We operate three independent research rooms behind the barrier on the 2nd floor of the East Campus Research Facility (ECRF): an animal breeding colony of NSG mice, an experimental procedure room, and an MRI suite.

Animal Breeding Colony

  • PATh maintains its own breeding colony of NSG mice
  • Restricted access to maintain integrity/health of the colony
  • PPE required at all times to maintain sterile working environment
  • Dedicated laminar flow stations for cage transfers and handling
  • Currently available strains are NSG and NSG expressing IL6 human transgene

Animal Procedure Room

  • PATh has a dedicated biosafety cabinet and anesthesia equipment for PDX mice
  • PATh operates this room following all BSL-2 protocols
  • Animals used in procedure room come from PATh breeding colony to maintain hygienic integrity of all experimental animals

MRI Suite

  • Aspect Imaging M3 High Resolution Compact MRI (1T)
  • Specifically designed to image mice
  • MRI is located behind the barrier to prevent spread of infection to NSG mice
  • MRI can scan using T1 or T2 weighted images and can track tumor progression and metastases
  • MRI uses a permanent magnet which allows for minimal servicing and almost 100% uptime

Facility Services

Surgical Services

While PATh’s chief purpose is to provide a comprehensive pre-clinical platform to reliably develop cancer models and test novel therapeutics, we understand that there may not always be a need for all the services that are offered. Therefore, we also offer our PDX services in an a la carte fashion. Second, the PATh facility has over twenty years of small animal surgical experience with a wide variety of expertise. Listed below are some of the core competencies that PATh can perform along with a willingness to try novel procedures that may be necessary to complete experiments. Budgets for surgical procedures can be created after a consultation to discuss investigator needs.

Telemeter Implantation

  • Carotid placement
  • Femoral placement
  • Abdominal aorta placement
  • Intraperitoneal placement

Brain Surgeries

  • Injection of virus (Ad, AAV, Lenti) to specific regions
  • Placement of cannula

General Procedures & Surgeries

  • Osmotic pump implantation (subQ or IP)
  • Ovariectomy
  • Vasectomy
  • Myocardial infarction
  • Intravenous infusion
  • Tail vein, subcutaneous, Intraperitoneal, Intramuscular injections
  • Simple metabolic cages (water intake, urine collection, food consumption)

Other Services

Project planning and management

We will work with our client to create an individualized project plan for their proposed xenograft work. We will establish the proper roles/responsibilities for each of the facility staff and the deliverables our clients are responsible for to compete the necessary work. We will work closely with our client to help design a study that will meet their budgeting and time related needs.

Tissue/cell implantation

We will implant tissue or cell line samples based on client specifications. We can perform routine engraftment strategies such as subcutaneous implantation, and orthotopic models as well. Any procedure that we have not attempted previously will require a feasibility study to investigate the probability of success.

Post engraftment characterization/study

Based upon the project planning and experimental design consultation we will execute all commonly performed post engraftment procedures including but not limited to tumor growth monitoring, compound/drug delivery, and tumor harvesting.

Tissue/Cell Implantation

  • Primary tumor implantation
  • Tumor passaging
  • Subcutaneous
  • Intravenous
  • Orthotopic models

Drug/Compound Delivery

  • Common routes of administration: PO, IV, IP, IM
  • Flexible dosing schedules

Tumor monitoring

  • Caliper Measurements
  • High Resolution MR Imaging
  • Volumetric analyses using Invicro Autoquant image analysis software (see Fig. 1 below)

Tissue Collection

  • Tumor/Organ collection, flash frozen in LN2 or formalin fixed
  • Terminal bleeds
PATh PDX Facility Four Week Course
Fig. 1: Four week timecourse of tumor progression, of a single mouse with a subcutaneous canine B-cell lymphoma implanted on one flank. Panel one is a pre-scan of the mouse before primary tumor implantation, and each subsequent panel is one additional week after implantation, up to 4 weeks. The primary tumor is highlighted in red, infiltrating tumor in green, and a metastasis in blue. Volume measurements are color coded above.

Using the Facility

Step by Step

  1. Consultation
    The first step in using PATh is an initial intake appointment to determine the specific data and outcome measures the client needs. All work performed within the PATh facility rooms will be performed by our staff. After our initial consultation a preliminary budget will be created and submitted for review to the client.
     
  2. Institutional Animal Care and Use Committee (IACUC) Amendment
    If a study plan has been agreed upon an IACUC amendment will be initiated to add the experiment and all procedures/substances necessary to complete the work. PATh maintains its own IACUC protocol for all work performed by its staff. The study design will be discussed in detail with the client, and work will proceed once the amendment has been approved.
     
  3. Study/Trial
    Deliverables (i.e. drug compounds, etc…) are the responsibility of the client and will be discussed in advance to allow enough time to be formulated or ordered prior to the beginning of the experiment. All discussed data points and procedures will be collected and performed; a study design may be incrementally amended during the experiment so long as it does not significantly interfere with the overall plan or violate any rules set in place by the Center for Animal Resources and Education (CARE) and IACUC.
     
  4. End of Study/Reimbursement
    All study data and collected materials will be due to the client within 30 days after the experiment has been completed. A final invoice will be compiled for all work completed and will be delivered to the client at that time. If the proposed work is a long term case study, then a payment schedule will be discussed at the time of initial consultation.

 

Publications

Recent Publications

  1. Methionine metabolism controls the B cell EBV epigenome and viral latency. Cell Metab. 2022 Sep 6;34(9):1280-1297.e9. PMID: 36070681
  2. Combined EZH2 and Bcl-2 inhibitors as precision therapy for genetically defined DLBCL subtypes. Blood Adv. 2020 Oct 27;4(20):5226-5231. PMID: 33104794
  3. Exploring the In Vivo and In Vitro Anticancer Activity of Rhenium Isonitrile Complexes. Inorg Chem. 2020 Jul 20;59(14):10285-10303. PMID: 32633531
  4. MYC Controls the Epstein-Barr Virus Lytic Switch. Mol Cell. 2020 May 21;78(4):653-669.e8. PMID: 32315601
  5. Epigenetic reprogramming sensitizes immunologically silent EBV+ lymphomas to virus-directed immunotherapy. Blood. 2020 May 21;135(21):1870-1881. PMID: 32157281

 

Contact Us

Rishi Puri
PATh Project Manager
Department of Biomedical Sciences
T8 010 Veterinary Research Tower
College of Veterinary Medicine
Cornell University
Ithaca, New York 14853

e. rp422@cornell.edu