MENTORED PATIENT ORIENTED RESEARCH CAREER DEVELOPMENT AW

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(Adapted from the applicant's abstract): The use of monoclonal antibody constructs as effectors and vectors of cytotoxic-mediating molecules are regaining attention as progress in molecular biology improves the investigators' understanding of alterations that are important in tumorigenesis. Similarly, advances in selection of cell surface molecules and drug delivery have enhanced the likelihood of deriving benefit from this antineoplastic approach. The proposed studies will make use of different strategies for selective delivery via antibody to preferentially target malignant cells. The specific aims of these studies are to: 1) explore the use of monoclonal antibodies as inhibitors of angiogenesis; 2) explore the use of targeted delivery of toxins as an anti-tumor strategy; and 3) explore selective tumor delivery of antibody-directed superantigen to enhance host response to tumors. The first study will assess the pharmacokinetics of a humanized antibody and evaluate its ability to localize at tumor sites. The unique target for this antibody is tumor induced neovascularization. In a second planned trial, Dr. Posey will evaluate the safety, schedule of administration, immune response, and preliminary activity of an antibody fragment to selectively deliver a potent bacterial toxin to tumor tissue. The third trial involves the use of an antibody fragment chemically linked to a superantigen in patients with incurable breast cancer. The optimum dose, immune response, and anti-tumor response will be determined. Dr. Posey will conduct these trials under the mentorship of Dr. Albert F. LoBuglio, Director of UAB's Comprehensive Cancer Center. Despite recent advances, there are still numerous unanswered questions that will require combining clinical research efforts and basic science to develop effective anti-noeplastic therapy. With renewed enthusiasm in industry and advances in recombinant technology, new promising agents are emerging that require development by skilled investigators. This grant award will be pivotal to Dr. Posey's progress on becoming a skilled independent investigator capable of competing for future support.