The Antitumor Assessment Core Facility was established in 2003 to provide highly qualified services to foster cancer research and to support early discovery of effective antitumor agents and regimens of therapies at Memorial Sloan-Kettering Cancer Center. In particular, the facility provides resources, professional and technical expertise, and advisory services related to the evaluation of agents with potential therapeutic activity. The facility works closely with investigators to establish in vivo mouse models; design and execute pharmacokinetic, toxicity, and in vivo efficacy studies; and determine the best formulation, administration route, and treatment schedule for each new compound, either alone or in combination with other agents.
Technical and Advisory Services Provided
- Cell lines and tumor tissues: We maintain a large repository of commonly used murine and human cell lines and tumor tissues.
- Xenografts: We establish xenograft models from cell lines or tumor samples provided by the investigator or supplied through our repository. Methodologies for cell/tissue implantation include subcutaneous, intraperitoneal, intravenous, intracardiac, and orthotopic (lung, liver, pancreas, spleen, kidney, bladder, bone, brain, prostate, mammary fat pads, ovary).
- Patient-derived xenografts (PDX): We establish xenograft models and cell lines directly from patient tumor samples obtained during surgery/biopsy. Successfully engrafted tumors are propagated by serial transplantation and cryopreserved for future use.
- Efficacy studies: We evaluate in vivo efficacy of agents either alone or in combination with standard chemotherapy regimens against murine tumors, human tumor xenografts, and transgenic mouse models of human cancer. Tumor size is monitored by caliper measurement (for subcutaneous xenografts) and/or in vivo imaging (for disseminated and orthotopic models).
- Compound formulation/delivery: Compounds are formulated for in vivo delivery using a variety of commonly used vehicles and are administered by a number of routes, including oral gavage, intravenous, intraperitoneal, subcutaneous, and intratumor, and by food and/or drinking water. Additionally, Alzet osmotic minipumps are implanted for continuous drug delivery, and slow-release hormone pellets are implanted subcutaneously.
- Rodent toxicology: Determination of maximum-tolerated dose after single dose or chronic exposure required for tolerance profiling of candidate agents.
- Rodent toxicology: Acute single-dose or repeat-dose toxicity studies in support of Investigational New Drug Applications.
- PK/PD studies: Upon compound administration (in mice, rats, and dogs), plasma, organs, and tumor samples are collected at multiple time points to assess bioavailability and pharmacokinetic/pharmacodynamic profile of therapeutic agents.
- Data management: The facility provides computerized comprehensive management of all experimental data, digital photography of experimental animals and samples, and on-the-spot biostatistical support.
- Consultation: The facility head provides assistance with experiment design and data analysis, IACUC Protocols preparation, writing of manuscripts, grant applications, and pharmacology/toxicology sections of Investigational New Drug Applications.
- Technical assistance: The facility provides technical assistance on all aspects of in vivo studies, including rodent surgeries, tumor cell implantation, tumor transplantation, bone marrow transplants, drug formulation and administration (e.g., intravenous, intraperitoneal, oral, intratumor, subcutaneous), radiation therapy, x-ray, IVIS, Maestro, MRI and PET imaging, hematology and clinical chemistry analyses, collection of fluids (e.g., blood, urine), and collection and preservation of tissues/organs for either RNA/protein or HIC analysis.
Services of the Antitumor Assessment Core Facility are available on a first-come, first-served basis to all investigators at Memorial Sloan-Kettering. All requests for services must first be approved by the facility head, who also helps investigators in planning the studies to be conducted and provides them with an estimate of the final cost. Specialized requirements of individual investigators are considered on a case-by-case basis following evaluation of feasibility by the facility management.