NOVEL BIOACTIVE LIPID DERIVATIVES, AND METHODS OF MAKING AND USING THE SAME

摘要

Compositions and methods for producing monoclonal antibodies and their derivatives reactive against bioactive lipid targets are described. These compositions include derivatized lipids, each of which comprises a bioactive lipid that having a polar head group and at least one hydrocarbon chain (e.g., a lysolipid such as lysophosphatidic acid or sphingosine-1-phosphate) in which a carbon atom has been derivatized with a pendant reactive group; immunogens made by linking a derivatized lipid to a carrier moiety (e.g., a carrier protein, polyethylene glycol, colloidal gold, alginate, or a silicone bead); monoclonal antibodies and derivatives produced by immunizing an animal with such an immunogen; and therapeutic and diagnostic compositions containing such antibodies and antibody derivatives. Methods for making such derivatized lipids, immunogens, and monoclonal antibodies and derivatives, methods for detecting such antibodies once generated, and therapeutic and diagnostic methods for using such antibodies and derivatives, are also described.

主权项

1. A method, comprising:
a. immunizing an immune competent non-human mammalian host with an amount of a derivatized bioactive lipid conjugate sufficient to elicit antibody production in the immune competent non-human mammalian host to the bioactive lipid component of derivatized bioactive lipid conjugate, wherein the derivatized bioactive lipid conjugate comprises a derivatized bioactive lipid that comprises a bioactive lipid having a head group and at least one hydrocarbon chain covalently linked to the head group, wherein a carbon atom within the hydrocarbon chain is derivatized with an optionally protected pendant reactive group to form the derivatized bioactive lipid, and a carrier moiety conjugated to the derivatized bioactive lipid via the pendant reactive group; and b. identifying antibody-producing cells isolated from the immune competent non-human mammalian host that produce antibody specifically reactive with the bioactive lipid of the derivatized bioactive lipid conjugate, wherein the identification comprises using a support, optionally a solid support, modified with the derivatized bioactive lipid to detect cells that produce antibody specifically reactive with the bioactive lipid.