Ceacam1 based cancer therapy and diagnosis

Abstract

The invention relates to methods and compositions for the treatment and diagnosis of cancers. At least one aspect of the present invention relates to methods and compositions for enhancing the efficacy of tumor-infiltrating lymphocyte (TIL) therapy in the treatment of cancer by negatively modulating the activity of the CEACAM1 protein.

What is claimed is: 
     
         1 . A method for enhancing the efficacy of Tumor Infiltrating Lymphocyte cancer therapy comprising the modulation of CEACAM1 protein function. 
     
     
         2 . The method of  claim 1 , wherein said modulation of CEACAM1 protein function comprises the disruption of a target CEACAM1 homotypic or heterotypic protein-protein interaction. 
     
     
         3 . The method of  claim 2 , wherein the disruption of said target CEACAM1 homotypic or heterotypic protein-protein interaction comprises contacting at least one protein involved in said protein-protein interaction with an inhibitory agent that partially or completely inhibit or disrupt said protein-protein interaction, said inhibitory agent comprising an amino acid sequence, nucleic acid sequence, small molecule compound, or combinations thereof. 
     
     
         4 . The method of  claim 2 , wherein the disruption of said target CEACAM1 homotypic or heterotypic protein-protein interaction comprises contacting at least one protein involved in said protein-protein interaction with an inhibitory agent that partially or completely inhibits or disrupts said protein-protein interaction, said inhibitory agent comprising an amino acid sequence derived from a CEACAM family protein sequence. 
     
     
         5 . The method of  claim 2 , wherein the disruption of said target CEACAM1 homotypic or heterotypic protein-protein interaction comprises contacting at least one protein involved in said protein-protein interaction with an inhibitory agent that partially or completely inhibits or disrupts said protein-protein interaction, said inhibitory agent comprising an immunoglobulin or fragment thereof. 
     
     
         6 . The method of  claim 2 , wherein the disruption of said target CEACAM1 homotypic or heterotypic protein-protein interaction comprises contacting at least one protein involved in said protein-protein interaction with an inhibitory agent that partially or completely inhibits or disrupts said protein-protein interaction, said inhibitory agent comprising an amino acid sequence derived from a CEACAM family protein sequence. 
     
     
         7 . The method of  claim 2 , wherein the disruption of said target CEACAM1 homotypic or heterotypic protein-protein interaction comprises contacting at least one protein involved in said protein-protein interaction with an inhibitory agent that partially or completely inhibits or disrupts said protein-protein interaction, said inhibitory agent conjugated with a protein-crosslinking moiety. 
     
     
         8 . The method of  claim 1 , wherein said method is performed in situ, in vivo, or in vitro. 
     
     
         9 . The method of  claim 1 , wherein said method is performed in a cell culture comprising a population of Tumor Infiltrating Lymphocytes. 
     
     
         10 . A method for enhancing the efficacy of Tumor Infiltrating Lymphocyte cancer therapy comprising decreasing the effective concentration of CEACAM1 functional protein. 
     
     
         11 . The method of  claim 10 , wherein said method comprises the inhibition of CEACAM1 gene expression, protein synthesis, protein stability, or combinations thereof. 
     
     
         12 . The method of  claim 10 , wherein said method is performed in a cell culture comprising a population of Tumor Infiltrating Lymphocytes. 
     
     
         13 . A method for enhancing the efficacy of Tumor Infiltrating Lymphocyte cancer therapy comprising the enrichment of a Tumor Infiltrating Lymphocyte cell population for cells lacking CEACAM1. 
     
     
         14 . The method of  claim 13 , wherein said method comprising contacting said Tumor Infiltrating Lymphocyte cell population with a CEACAM1 binding element, said binding element labeled with a detectable moiety, an affinity-tag moiety, or both. 
     
     
         15 . The method of  claim 14 , wherein said CEACAM1 binding element is an anti-CEACAM1 immunoglobulin or fragment thereof. 
     
     
         16 . The method of  claim 13 , wherein said Tumor Infiltrating Lymphocyte cell population is subjected to affinity purification, cell sorting, or both. 
     
     
         17 . The method of  claim 13 , wherein said Tumor Infiltrating Lymphocyte cell population is contacted with an anti-CEACAM1 immunoglobulin and complement. 
     
     
         18 . The method of  claim 13 , wherein said Tumor Infiltrating Lymphocyte cell population is contacted with a CEACAM1 binding element conjugated to a cell toxin. 
     
     
         19 . A method for treating cancer in a human patient, said method comprising the step of administering to the patient a therapeutically effective amount of a composition comprising a CEACAM1 binding agent conjugated to a chemotherapeutic. 
     
     
         20 . The method of  claim 19 , wherein the CEACAM1 binding agent comprises an amino acid sequence derived from a member of the CEACAM protein family. 
     
     
         21 . The method of  claim 19 , wherein the CEACAM1 binding agent comprises an anti-CEACAM1 immunoglobulin or fragment thereof. 
     
     
         22 . The method of  claim 19 , wherein the CEACAM1 binding agent comprises a peptidomimetic or small molecule compound. 
     
     
         23 . The method of  claim 19 , wherein said chemotherapeutic comprises a cytotoxin, a chemokine, a pro-apoptotic, interferon, a radioactive moiety, or combinations thereof. 
     
     
         24 . The method of  claim 19 , wherein said chemotherapeutic moderates cellular metabolism. 
     
     
         25 . The method of  claim 19 , wherein said chemotherapeutic moderates nucleic acid metabolism, protein metabolism, cell division, DNA replication, purine biosynthesis, pyrimidine biosynthesis, amino acid biosynthesis, gene expression, mRNA processing, protein synthesis, apoptosis, or combinations thereof. 
     
     
         26 . A method for diagnosing a cancer in a human patient, said method comprising the step of contacting a biological sample derived from said patient with a CEACAM1 binding agent conjugated to a detectable moiety. 
     
     
         27 . The method of  claim 26 , wherein the CEACAM1 binding agent comprises an amino acid sequence derived from a member of the CEACAM protein family. 
     
     
         28 . The method of  claim 26 , wherein the CEACAM1 binding agent comprises an anti-CEACAM1 immunoglobulin or fragment thereof. 
     
     
         29 . The method of  claim 26 , wherein the CEACAM1 binding agent comprises a peptidomimetic or small molecule compound. 
     
     
         30 . The method of  claim 26 , wherein said detectable moiety comprises a fluorescent molecule, or a radioactive molecule, or a magnetic particle, or some combination thereof. 
     
     
         31 . A method for diagnosing a cancer in a human patient, wherein said method comprises the step of injecting into said patient a CEACAM1 binding agent conjugated to a detectable moiety. 
     
     
         32 . The method of  claim 31 , wherein the CEACAM1 binding agent comprises an amino acid sequence derived from a member of the CEACAM protein family. 
     
     
         33 . The method of  claim 31 , wherein the CEACAM1 binding agent comprises an anti-CEACAM1 immunoglobulin or fragment thereof. 
     
     
         34 . The method of  claim 31 , wherein the CEACAM1 binding agent comprises a peptidomimetic or small molecule compound. 
     
     
         35 . The method of  claim 31 , wherein said detectable moiety comprises a radioactive molecule. 
     
     
         36 . The method of  claim 31 , wherein said CEACAM1 binding agent conjugated to a detectable moiety is ingested by said human patient.