The facility provides resources, professional and technical expertise and advisory services related to the evaluation of agents with potential antitumor activity. Typical agents studied include cytotoxic antimetabolites; DNA-damaging agents and natural products; immunomodulating agents; cytotoxic antibodies and immunoconjugates; inducers of differentiation and cytostatics directed at tumor specific targets; and therapeutic cytokines and ionizing radiation.

The services of the facility include testing of agents or combinations of agents for their antiproliferative and/or cytotoxic effects in cell culture against one or more available murine and human tumor cell lines. These studies will utilize one of several different protocols using automated colorimetric or fluorescence detection technology, depending upon the agent and type of information sought. An exceedingly large number of rodent and human tumor cell lines are available in our frozen repository for these studies.

Candidate or test agents are also evaluated in vivo in model tumor systems of rodent origin and against human tumor xenografts in mice, as well as in transgenic models obtained by outsourcing or in-house acquisition when requested. These systems allow evaluation of each agent alone or in combination with other agents by different routes or different schedules of administration following preliminary toxicology to determine tolerance of mice to the agent(s). A very large number of rodent and human tumors are available in our frozen repository for these studies.

Technical and Advisory Services Provided

• Evaluation of candidate cytostatic/cytotoxic agents alone or in combination against tumor cells in culture. Studies are often carried out with cell lines engineered to increase or decrease expression of genes of interest either by sense or antisense cDNA transfection, and dominant-negative or knock-out technology. These cell lines are provided by the investigator or outsourced.

• Evaluation in vivo of agents alone or in combination against murine tumors, human tumor xenografts, and transgenic mouse models of human cancer. Genetically engineered tumor variants for transplantation focusing on genes of interest are provided by the investigator or outsourced.

• Small animal toxicology and histopathology required for tolerance profiling of candidate agents or in support of an IND application. Similar studies in rabbits are done by special arrangement.

• Formulation of therapeutic agents for parental or oral use in animals.

• Bioavailability and pharmacokinetic assessment of therapeutic agents in mice required for pharmacologic profiling or in support of an IND application.

• Computerized data management, digital photography of experimental animals, and on-the-spot biostatistical support.

• Frozen murine and human tumor repository.

• Outsourcing of transgenic mice from commercial or institutional vendors.

• Animal Research Protocol preparation, experimental design consultation, and technical assistance (rodent surgeries, tumor implantation, drug administration, bleeding, etc.) on all aspects of experimental therapeutics and on the drug development process.

Services of this facility are available of a first-come first-served basis to all investigators at the Center. Planning of studies to be conducted are the joint responsibility of the investigator requesting the services and the facility management. Because of the nature of the experimental process involved, these studies could represent a relatively significant effort on the part of the facility. Specialized requirements of individual investigators will be considered on a case-by-case basis following evaluation of feasibility by the facility management. All requests for services must first be approved by the facility head.

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