Antibody - Pretargeted Cytokine Therapy of Cancer
Abstract
We hypothesize that the selective accumulation of systemically administered cytokines at tumor sites can alter tumor microenvironments to favor the induction of anti-tumor immune responses. We further hypothesize that this can be accomplished by pre-targeting tumors with antibody streptavidin immunoconjugates and then administering biotinylated cytokines. The purpose of this research program is to identify antibody-pretargeted cytokine therapy strategies that lead to tumor-selective cytokine accumulation, the development of host inflammatory cell infiltrates in tumor, and the induction of tumor- specific immunity. The ultimate goal of this research is to identify candidate strategies for clinical development, alone or in combination with tumor vaccines. In the first year of this award we have made significant progress toward achieving these goals. Interleukin-2 (IL-2) has been biotinylated, and its biological properties have been thoroughly characterized. We have obtained a streptavidin-conjugated monoclonal antibody that recognized the Ep-CAM tumor antigen that is frequently overexpressed in breast cancer specimens. Animal experiments to characterize the biodistribution properties of the antibody - streptavidin conjugate and of the conjugate admixed with biotinylated IL-2 are underway, and pretargeting experiments are about to commence.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2000
- Accession Number
- ADA382515
Entities
People
- Louis Weiner
Organizations
- Fox Chase Cancer Center