Biomira, Inc.

Wisconsin Alumni Research Foundation

University of Alberta

Glen S. Kwon

Afsaneh Lavasanifar

John Samuel

B Michael Longenecker

Glen S Kwon

Glen Kwon

Provided are methods and compositions for reducing the toxicity of certain hydrophobic therapeutic agents, especially polyene antibiotics, in particular, Amphotericin B (AmB), and therapeutics such as paclitaxel, tamoxifen, an acylated prodrug or an acylated cis-platin, by incorporating these agents within micelles comprising an amphiphilic block-forming copolymer. Where the polyene is amphotericin B, desirably the spacer is an alkyl molecule of aabout 2 to about 8 carbon atoms, desirably 6 carbon atoms, and the core is an N-alkyl molecule of about 8 to about 28 carbon atoms, desirably 12 to 22 carbon atoms, advantageously, 12 to 18 carbon atoms, and as specifically embodied, 18 carbon atoms (stearate moiety). For the formulation of a larger polyene, the spacer and core are proportionately larger than those for amphotericin B. As specifically exemplified herein, the polymer backbone is a PEO of about 270 units with about 10-30 core-forming PLAA subunits, and advantageously about 14-24. Desirably the stearate moiety has a substitution level on the copolymer from about 35 percent to about 70 percent.

Methods and compositions for polyene antibiotics with reduced toxicity

A method is provided for treating a Th1 mediated disease state by administration to a subject of a slow release vehicle such as a liposome or microsphere formulation containing an antigenic peptide and a Th1 specific immunomodulator wherein the antigenic peptide contains a T cell epitope and is released from the vehicle at a rate in the range from about 10 to 2 weight percent of the peptide in 24 hours at 37&deg; C.

Method for eliciting Th1-specific immune response

A heterologous sandwich immunoassay has been developed for human TF antigen using a monoclonal antibody as the catcher and labelled peanut agglutinin as the probe. Since human TF antigen is shed by tumor cells, a positive determination of the TF antigen in a patient sample indicates the presence of cancer. The test can also be used to monitor the course of conventional chemotherapy or radiotherapy by monitoring the amount of TF antigen in a fluid sample from a patient being so treated. Because of the sensitivity of the assay method, cancer can be detected in very early stages by the assay method of the present invention.

Lectin-antibody immunoassays for TF epitope-bearing antigens

Human tumor associated Thomsen-Friedenreich (TF) antigen is purified from adenocarcinoma conditioned media, adenocarcinoma cell detergent extracts or plural effusion fluid by affinity chromatography using an insolubilized TF-specific monoclonal antibody, MAb 49H.8. The TF antigen is a glycoprotein characterized by a non-cryptic Gal .beta.(1.fwdarw.3) GalNAc epitope, a molecular weight in excess of 1,000,000 daltons, and extractability with perchloric acid, the epitope being sensitive to alkali and periodate but resistant to acid. A heterologous sandwich immunoassay has been developed for human TF antigen using a monoclonal antibody as the catcher and labelled peanut agglutinin as the probe. Since human TF antigen is shed by tumor cells, a positive determination of the TF antigen in a patient sample indicates the presence of cancer. The test can also be used to monitor the course of conventional chemotherapy or radiotherapy by monitoring the amount of TF antigen in a fluid sample from a patient being so treated. Because of the sensitivity of the assay method, cancer can be detected in very early stages by the assay method of the present invention.

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Edmonton, Canada

John Samuel