Carbohydrate-containing pan cancer marker

Abstract

The effective epitope of CA215, a known cancer marker and antigen, has been demonstrated to include a carbohydrate moiety of defined composition and to be non-reactive with anti-human IgG, IgA and IgM, although CA215 is an immunoglobulin heavy chain-like molecule. The defined epitope may be used to prepare immunogenic compositions for treatment and prevention of cancers in humans and may be optimized as to protocol and formulation in animal model systems. Improved protocols for diagnosis and treatment are also described.

1 . A method to elicit an immune response to cancer in a subject, wherein said cancer expresses CA215, which method comprises administering to said subject a formulation comprising a molecule that is immunoreactive with RP215 monoclonal antibody, but not significantly immunoreactive with antihuman IgG, said molecule consisting of an FR1 and CDR1 sequence of CA215 and a carbohydrate, wherein said carbohydrate is coupled to a threonine or serine glycosylation site proximal to the junction between FR1 and CDR1. 
     
     
         2 . The method of  claim 1  wherein said molecule is coupled to a heterologous moiety. 
     
     
         3 . The method of  claim 1 , wherein the subject is human and which method further comprises treating said subject with chemotherapeutic agents or with radiation. 
     
     
         4 . The method of  claim 1 , wherein the subject is an animal tumor model. 
     
     
         5 . A method to elicit an immune response to cancer in a subject, wherein said cancer expresses CA215, which method comprises administering to said subject a formulation comprising antiidiotype antibodies to RP215 monoclonal antibody. 
     
     
         6 . The method of  claim 5 , wherein the subject is human and which method further comprises treating said subject with chemotherapeutic agents or with radiation. 
     
     
         7 . The method of  claim 5 , wherein the subject is an animal tumor model. 
     
     
         8 . A method to detect CA215 in a sample, which method comprises
 (a) contacting said sample with a solid support to which is bound an anti-human IgG, followed by contacting said support with the monoclonal antibody RP215 or an antibody cross-reactive therewith or with immunospecific fragments of either, that is labeled or modified subsequently to contain a label; or   (b) conducting a sandwich immunoassay in which one member of the sandwich is RP215 antibody and the other member of the sandwich is immunoreactive with antihuman IgG.   
     
     
         9 . A protocol for diagnosis and treatment of solid tumors in a human patient which method comprises
 a) diagnosing said patient by assaying a sample of body fluid from said patient for the presence or absence of CA215, wherein the presence of CA215 indicates the presence of a solid tumor in said patient; and   b) treating said patient by administering to said patient a humanized antibody that binds an epitope on membrane-bound CA215.   
     
     
         10 . The method of  claim 9 , wherein the antibody is a humanized form of RP215. 
     
     
         11 . The method of  claim 9 , wherein the antibody is coupled to a cytotoxic agent.