PROJECT SUMMARY (See instructions): The role of immunotherapy in the portfolio of cancer therapeutics is growing rapidly. The recent FDA approvals of the Provenge vaccine for prostate cancer and the anti-CTLA-4 mAb ipilimumab for melanoma have spurred expanded exploration of new immunotherapeutics in cancer patients. The specific recognition of tumor antigens by CD8* T cells and the binding of monoclonal antibodies to tumor targets represent the main effector mechanisms for immune-mediated tumor rejection. The exquisite specificity of these interactions has earned cancer immunotherapy the designation as a targeted therapy. Recent work on predictive biomarkers associated with clinical benefit from immunotherapies is expanding the notion of immunotherapy further as a patient-specific therapy. The tremendous progress made over the past decade is to a large extent due to the successful application of bidirectional translational research. Rational development of immunotherapies has benefitted from careful analysis of scientific endpoints from patient material. The main purpose of the Human Immunologic Monitoring-cGMP (HIM-cGMP) Facility is to provide the resources to enable UCCCC investigators to conduct novel immunotherapy clinical trials. Improving upon the effectiveness of current agents, developing new immunotherapeutic interventions (such as anti-cancer vaccines), and elucidating the mechanism of success versus failure of investigational treatments, all require careful monitoring of scientific endpoints. The HIM-cGMP Facility serves as a specialized laboratory for evaluating pharmacodynamic parameters in response to agents or interventions that impact on immune cells. The integration of the cGMP Subcore enables the preparation of clinical grade products, such as cancer vaccines, for administration to patients. The Facility also monitors biologic effects of other pharmacologic agents (such as signal transduction inhibitors) using lymphocytes or other hematopoiefic cells as a surrogate tissue. The HIM-cGMP Facility therefore lies at the heart of the UCCCC's clinical/translational effort in cancer immunotherapy, and is vital for the scientific investigation of additional novel agents.

RELEVANCE (See instructions): Development of new effective immunotherapies as cancer therapeutics has benefited from bi-translational research. The HIM-cGMP Facility functions directly to support translational clinical trials directly in cancer patients and is, therefore, completely immersed in efforts to improve the outcome of patients with cancer.