Diagnosis of cancer using tumor-mimetic cell surface antigen from chemically modified normal cells
OwnerMadhao B. Sahasrabudheinventor
Life of this patent
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Abstract
A tumor-mimetic cell surface antigen (TMCSA) is produced by chemical treatment of normal human cells with a nucleophilic reagent which causes a hydrophobic-hydrophilic interconversion at the cell surface, such as a halobenzene derivative or a benzene sulfonate derivative. This TMCSA cross-reacts with tumor antigens from every type of tumor examined of any histopathologic type. Cancer is detected by detecting the presence of lymphocytes sensitized to tumor antigens based on their reactivity with TMCSA in a binding assay or lymphocyte stimulation or migration inhibition assay.
Claims20
A method for detecting the presence of a non-leukemia form of cancer in a subject having lymphocytes sensitized to a tumor antigen, which method comprises
- (a) obtaining a sample of blood from said subject;
- and
- (b) assaying the reactivity of leucocytes of said sample in vitro with a tumor-mimetic cell surface antigen (TMCSA) which TMCSA is produced by treating cells with a chemical agent which is a nucleophilic reagent with one leaving group and between one and three electron-withdrawing groups having one or more of the following properties when the cells are treated at a temperature and pH which are non-toxic:
- (i) converts hydrophilic sites to hydrophobic sites on the surface of said cells;
- (ii) causes a gain or loss of HLA antigens on the surface of said cells;
- or
- (iii) causes a change to the surface of leukocytes similar to changes induced by fluorodinitrobenzene under substantially similar conditions
- wherein said TMCSA is in the form of either:
- (A) intact normal human cells which have been chemically treated with said chemical agent such that TMCSA is present on their surface;
- (B) solubilized membranes of said treated cells of (A);
- or
- (C) affinity purified TMCSA produced from said solubilized membranes of (B) using a TMCSA-specific antibody,
- wherein the detection of reactivity with said TMCSA indicates the presence of said non-leukemia form of cancer in said subject.
A method for detecting the presence of lymphocytes in a subject which are sensitized to a tumor antigen and are reactive with TMCSA, which method comprises
- (a) obtaining a sample of blood from said subject;
- (b) assaying in vitro
- (i) reactivity other than antibody secretion, or
- (ii) binding
- of leucocytes of said sample with a TMCSA produced by treating cells with a chemical agent which is a nucleophilic reagent with one leaving group and between one and three electron-withdrawing groups;
- having one or more of the following properties when the cells are treated at a temperature and pH which are non-toxic:
- (A) converts hydrophilic sites to hydrophobic sites on the surface of said cells;
- (B) causes a gain or loss of HLA on the surface of said cells;
- or
- (C) causes a change to the surface of leukocytes similar to changes induced by fluorodinitrobenzene under substantially similar conditions
- which TMCSA is in the form of either:
- (1) normal human cells which have been chemically treated with said chemical agent such that TMCSA is present on their surface;
- (2) solubilized membranes of said treated cells of (1);
- or
- (3) affinity purified TMCSA produced from said solubilized membranes of (2) using a TMCSA-specific antibody,
- wherein detection of reactivity or binding of said leucocytes with said TMCSA indicates the presence of said sensitized lymphocytes.
A method for monitoring therapy in a non-leukemia cancer patient to detect a therapeutic effect, which method comprises:
- (a) subjecting said patient to a cancer therapy;
- (b) obtaining a sample of blood from said patient at two or more time points during said therapy, after said therapy, or both;
- (c) assaying in vitro
- (i) reactivity other than antibody secretion, or
- (ii) binding
- of leucocytes of said sample with a TMCSA produced by treating cells with a chemical agent which is a nucleophilic reagent with one leaving group and between one and three electron-withdrawing groups;
- having one or more of the following properties when the cells are treated at a temperature and pH which are non-toxic:
- (A) converts hydrophilic sites to hydrophobic sites on the surface of said cells;
- (B) causes a gain or loss of HLA on the surface of said cells;
- or
- (C) causes a change to the surface of leukocytes similar to changes induced by fluorodinitrobenzene under substantially similar conditions
- which TMCSA is in the form of either:
- (1) normal human cells which have been chemically treated with said chemical agent such that TMCSA is present on their surface;
- (2) solubilized membranes of said treated cells of (1);
- or
- (3) affinity purified TMCSA produced from said solubilized membranes of (2) using a TMCSA-specific antibody,
- wherein a decrease in said reactivity or binding from one time point before, during or after therapy to a subsequent time point during or after therapy is an indication of a therapeutic effect.
A kit for use in an enzyme assay to detect the presence of lymphocytes sensitized to a tumor antigen, said kit being compartmentalized to receive in close confinement therein one or more containers, said kit comprising a first container containing a TMCSA preparation conjugated to an enzyme, which TMCSA comprises
- (a) normal human cells which have been chemically treated with chemical agent which is a nucleophilic reagent with one leaving group and between one and three electron-withdrawing groups having one or more of the following properties when the cells are treated at a temperature and pH which are non-toxic:
- (i) converts hydrophilic sites to hydrophobic sites on the surface of said cells;
- (ii) causes a gain or loss of HLA antigens on the surface of said cells;
- or
- (iii) causes a change to the surface of leukocytes similar to changes induced by fluorodinitrobenzene under substantially similar conditions
- (b) solubilized membranes of said treated cells of (a);
- or
- (c) affinity purified TMCSA produced from said solubilized membranes of (b) using an TMCSA-specific antibody,
- which preparation binds detectably to lymphocytes sensitized to a tumor antigen.
Dependencies are inferred from the claim text.