Beth Israel Deaconess Medical Center, Inc.

The Beth Israel Hospital Association

Harvard College

Donald R Senger

Harold F Dvorak

Michael Detmar

Kevin Patrick Claffey

The present invention provides a method for inhibiting tumor angiogenesis in a living subject. The method relies upon tumor angiogenesis mediated by vascular endothelial growth factor and specified induced integrin cell surface receptors expressed on the endothelial cells of tumor-included and tumor-associated blood vessels. The methodology also administers at least one antagonistic preparation effective against specified induced and expressed integrin heterodimers on the endothelial cell surface of the living subjects, the consequence of which results in an effective inhibition of tumor angiogenesis in-vivo.

Method for inhibiting tumor angiogenesis in a living subject

The present invention provides an immunological preparation comprising not less than two types of conjugate molecules in admixture for concurrent specific binding to a spatially exposed region of vascular permeability factor (VPF) bound in-vivo to a tumor-associated blood vessel. Each conjugate molecule type comprises at least a binding portion of an antibody specific for an epitope present within a spatially exposed region of bound VPF; and an effector moiety covalently bound to the specific binding portion. The immunological preparation has wide uses and applications including analytical studies, in-vivo diagnostic testing, and in-vivo therapeutic treatments.

Immunological preparation for concurrent specific binding to spatially

New compounds that bind specifically to vascular permeability factor (VPF) are used in methods of targeting these compounds, which include effector molecules that are, e.g., toxic, radioactive, or serve as marker labels, for tumor cells and the associated blood vessel endothelial cells, based on the discovery that VPF concentrates selectively in the endothelium and basement membrane lining tumor-associated blood vessels to a far greater degree than in normal vessels. By targeting VPF rather than the tumor cells themselves, the invention avoids the problems of tumor heterogeneity and diffusion distance.

Vascular permeability factor targeted compounds

Method to detect and/or determine the presence of cancer cells in mammals, including humans, and to monitor the progress of treatment for cancer. A human protein marker, the assay-marker, has been ascertained of the molecular weight 70,000-74,000, which is secreted by cancer cells at levels 10-fold or greater than that observed with normal cells. An assay is described where the assay-marker or an antigenically analogous protein, the analog-marker, is used to prepare antibodies to the assay-marker. The antibodies are then reacted with blood or serum samples to determine the level of the assay-marker in the sample. Thus, the assay essentially comprises (1) providing an antibody to the protein described above (2) reacting the antibody of step 1 with the sample to be tested and (3) measuring the level of the reacted antibody to detect and/or determine the presence and/or quantity of cancer cells.

Method of assaying the presence of cancer cells

A purified vascular permeability protein factor and method of manufacture, wherein the factor has the following characteristics:

Growing community of inventors

Medfield, MA, United States of America

Donald R Senger