ANTITUMOR ACTIVITY OF RECOMBINANT INTERLEUKIN I

  • Braunschweiger, Paul G, (PI)

Project: Research project

Description

The overall goal of this project is to define mechanisms involved in the
antitumor activity of human recombinant IL-1 in RIF-1 and Panc02 murine
tumor models, and to investigate new approaches to solid tumor therapy by
combining IL-1 and chemotherapy. Clonogenic cell survival and regrowth
delay endpoints will be used to determine dose and time dependent IL-1
mediated tumor cytotoxicity. Since IL-1 is not cytotoxic to RIF-1 cells, in
continuous culture, in vivo cytotoxicity is likely mediated by tumor host
cells. This hypothesis will be tested in studies to define the role of
tumor macrophages and their products (e.g. TNF) in IL-1 mediated tumor cell
kill in vivo. IL-1 mediated vascular and proliferative responses could influence the
effectiveness of other therapeutic modalities in solid tumors. Time and
dose response studies will be conducted to determine the effects of IL-1 on
blood flow, vascular patency tumor pH and water distribution in tumor and
normal tissues by isotope dilution methods. The regulatory role of adrenal
hormones and prostaglandins, in IL-1 mediated vascular responses, and the
importance of reduced tumor blood flow and tumor pH, in IL-1 mediated
cytotoxicity, will be studied. Since IL-1 might be used with other
modalities, the effect of immunosuppressive therapy (chemotherapy, surgery)
on IL-1 antitumor activity will be determined. The information from these
experiments will be used to design therapeutic strategies in which
chemotherapy (Cp, Adr, liposome encapsulated Adr) is applied to exploit
IL-1 mediated antitumor activities. These strategies will be tested in
RIF-1 and Panc02 tumors, using clonogenic cell survival and regrowth delay
endpoints. The results from these studies will provide the conceptual framework for
the use of IL-1, as a single agent and in combination with chemotherapy and
surgery, to improve the management of human malignancies.
StatusFinished
Effective start/end date9/1/898/31/93

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Interleukin-1
Neoplasms
Blood Vessels
Cell Survival
Vascular Patency
Drug Therapy
Therapeutics
Immunosuppressive Agents
Combination Drug Therapy
Human Activities
Liposomes
Isotopes
Prostaglandins
Cell Culture Techniques
Macrophages
Water

ASJC

  • Medicine(all)