Dr. Komschlies is a senior scientist with SAIC Frederick and works in collaboration with the Laboratory of Experimental Immunology (LEI) at the NCI in Frederick, MD. She received her Ph.D. in Immunology at the University of Connecticut, and performed postdoctoral studies on thymocyte differentiation with Dr. Bonnie J. Mathieson at the NCI-FCRDC.
Interleukin-7 (IL-7) is a pre-B cell growth factor and can stimulate/co-stimulate thymocytes, T-cell subsets and lines, enhance CTL and LAK generation and induce monocytes to secrete cytokines in vitro. These characteristics suggest that IL-7 may enhance T-cell-dependent vaccine responses to antigens from tumors or infectious agents and restore the lymphoid compartment in lymphopenic situations. Thus, it is important to determine the full potential of IL-7 as a biological response modifier for treatment of various diseases and to elucidate the mechanisms by which IL-7 acts.
We are examining the potential use of IL-7 in lymphoid reconstitution, enhancement of T-cell function and as an antitumor agent. Our studies have shown that IL-7 is able to accelerate donor-origin T-cell and B-cell engraftment following bone marrow transfer (BMT). Further, in vivo administration of IL-7 is able to: 1) increase T-cell numbers, especially those of the CD8+ subset, 2) enhance T-cell responses, and 3) reduce the number of lung metastases in a dose-dependent fashion. These findings suggest that IL-7 may be useful clinically in the treatment of iatrogenic lymphopenia, lymphoid reconstitution after BMT and AIDS, or as an adjuvant in immunization against cancer or infectious diseases in immunosuppressed/nonresponsive patients.
Thus, studies are in progress to determine the ability of exogenous IL-7 to enhance responses to specific antigen in vivo and, if successful, elucidate the mechanism of action. In particular, the ability of IL-7 to enhance immune and therapeutic responses to tumor-peptide vaccines is being studied. Syngeneic fibroblasts transfected with IL-7 as the in vivo source of IL-7 also are being used to avoid the logistical problems associated with systemic administration of IL-7 by focusing continuous IL-7 production at local vaccine sites. IL-7 may also be useful in restoring T-cell numbers and function in AIDS patients. Because IL-7 has been shown to have antitumor effects a Phase 1 single agent clinical trial in cancer patients has been proposed by Dr. Barry Gause, CRB, DCS. However, combinations of IL-7 with other cytokines may have greater utility and should be the focus of further studies and trials. Our overall goals for this project are to determine the potential use of IL-7 as a T-cell adjuvant in various vaccine settings, as an antitumor therapy and as a therapy for lymphoid cell restoration for use in human disease. Moreover, we wish to elucidate the cellular biological and molecular mechanisms by which IL-7 functions in these settings.
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Updated: July 1, 1996