Igf-1r antibody and its use for the diagnosis of cancer

Abstract

The present disclosure relates to IGF-IR (insulin like growth factor receptor-1) antibodies characterized by CDR sequences a, to be used in detection methods of IGF-IR expressing tumoral cells.

1 .- 15 . (canceled) 
     
     
         16 . A method for detecting in vitro or ex vivo the presence and/or the location of IGF-1R expressing tumor cells in a subject, the method comprising the steps of:
 (a) contacting a biological sample from the subject with an IGF-1R antibody, or an antigen-binding fragment thereof, the antibody comprising:   i) a heavy chain comprising the following three CDRs, respectively CDR-H1 of sequence SEQ ID No. 1, CDR-H2 of sequence SEQ ID No. 2 and CDR-H3 of sequence SEQ ID No. 3; and   ii) a light chain comprising the following three CDRs, respectively CDR-L1 of sequence SEQ ID No. 4, CDR-L2 of sequence SEQ ID No. 5 and CDR-L3 of sequence SEQ ID No. 6; and   (b) detecting the binding of the IGF-1R antibody, or antigen-binding fragment thereof, to the biological sample.   
     
     
         17 . The method according to  claim 16 , the antibody comprising a heavy chain variable domain of sequence SEQ ID No. 7, or any sequence with at least 90% of homology with the sequence SEQ ID No. 7; and/or a light chain variable domain of sequence SEQ ID No. 8, or any sequence with at least 90% of homology with the sequence SEQ ID No. 8. 
     
     
         18 . The method according to  claim 16 , wherein the antibody is secreted by the hybridoma deposited at the CNCM, Institut Pasteur, Paris, on Sep. 17, 2014, under number 1-4894. 
     
     
         19 . A method for detecting in vitro or ex vivo the percentage of tumor cells expressing IGF-1R in a subject, said method comprising the steps of:
 (a) contacting a biological sample from the subject with an IGF-1R antibody, or an antigen-binding fragment thereof, the antibody comprising:   i) a heavy chain comprising the following three CDRs, respectively CDR-H1 of sequence SEQ ID No. 1, CDR-H2 of sequence SEQ ID No. 2 and CDR-H3 of sequence SEQ ID No. 3; and   ii) a light chain comprising the following three CDRs, respectively CDR-L1 of sequence SEQ ID No. 4, CDR-L2 of sequence SEQ ID No. 5 and CDR-L3 of sequence SEQ ID No. 6; and   (b) quantifying the percentage of cells expressing IGF-1R in the biological sample.   
     
     
         20 . The method according to  claim 19 , the antibody comprising a heavy chain variable domain of sequence SEQ ID No. 7, or any sequence with at least 90% of homology with the sequence SEQ ID No. 7; and/or a light chain variable domain of sequence SEQ ID No. 8, or any sequence with at least 90% of homology with the sequence SEQ ID No. 8. 
     
     
         21 . The method according to  claim 19 , wherein the antibody is secreted by the hybridoma deposited at the CNCM, Institut Pasteur, Paris, on Sep. 17, 2014, under number 1-4894. 
     
     
         22 . A method for determining in vitro or ex vivo the expression level of IGF-1R in tumor cells in a subject, the method comprising the steps of:
 (a) contacting a biological sample from the subject with an IGF-1R antibody, or an antigen-binding fragment thereof, the antibody comprising:   i) a heavy chain comprising the following three CDRs, respectively CDR-H1 of sequence SEQ ID No. 1, CDR-H2 of sequence SEQ ID No. 2 and CDR-H3 of sequence SEQ ID No. 3; and   ii) a light chain comprising the following three CDRs, respectively CDR-L1 of sequence SEQ ID No. 4, CDR-L2 of sequence SEQ ID No. 5 and CDR-L3 of sequence SEQ ID No. 6; and   (b) quantifying the level of binding of the IGF-1R antibody, or an antigen-binding fragment thereof, to IGF-1R in the biological sample.   
     
     
         23 . The method according to  claim 22 , the antibody comprising a heavy chain variable domain of sequence SEQ ID No. 7, or any sequence with at least 90% of homology with the sequence SEQ ID No. 7; and/or a light chain variable domain of sequence SEQ ID No. 8, or any sequence with at least 90% of homology with the sequence SEQ ID No. 8. 
     
     
         24 . The method according to  claim 22 , wherein the antibody is secreted by the hybridoma deposited at the CNCM, Institut Pasteur, Paris, on Sep. 17, 2014, under number 1-4894. 
     
     
         25 . A method for determining in vitro or ex vivo the IGF-1R scoring of tumor cells or of a tumor in a subject, the method comprising the steps of:
 (a) contacting a biological sample from the subject with an IGF-1R antibody, or an antigen-binding fragment thereof, the antibody comprising:   i) a heavy chain comprising the following three CDRs, respectively CDR-H1 of sequence SEQ ID No. 1, CDR-H2 of sequence SEQ ID No. 2 and CDR-H3 of sequence SEQ ID No. 3; and   ii) a light chain comprising the following three CDRs, respectively CDR-L1 of sequence SEQ ID No. 4, CDR-L2 of sequence SEQ ID No. 5 and CDR-L3 of sequence SEQ ID No. 6;   (b) quantifying by Fluorescence Activated Cell Sorting (FACS) or immunohistochemistry (IHC) the level of binding of the IGF-1R antibody, or an antigen-binding fragment thereof, to IGF-1R in said biological sample; and   (c) scoring the tumor cells or the tumor by comparing the quantified level obtained in step (b) to an appropriate scale based on the intensity of the staining and the percentage of positive cells.   
     
     
         26 . The method according to  claim 25 , the antibody comprising a heavy chain variable domain of sequence SEQ ID No. 7, or any sequence with at least 90% of homology with the sequence SEQ ID No. 7; and/or a light chain variable domain of sequence SEQ ID No. 8, or any sequence with at least 90% of homology with the sequence SEQ ID No. 8. 
     
     
         27 . The method according to  claim 26 , wherein the antibody is secreted by the hybridoma deposited at the CNCM, Institut Pasteur, Paris, on Sep. 17, 2014, under number 1-4894. 
     
     
         28 . A method for determining whether an oncogenic disorder is susceptible to treatment with an inhibitor targeting the IGF-1R pathway, said method comprising the steps of:
 (a) determining in vitro or ex vivo the IGF-1R scoring of tumor cells or of a tumor of a subject according to the method of  claim 25 , and   (b) determining that, if the IGF-1R scoring of tumor cells or the tumor is IGF-1R(+), the oncogenic disorder is susceptible to treatment with an antibody drug targeting the IGF-1R pathway.   
     
     
         29 . The method of  claim 28  wherein said inhibitor is an IGF-1R antibody. 
     
     
         30 . The method of  claim 29  wherein the IGF-1R antibody is alone, combined or conjugated. 
     
     
         31 . A method for determining in vitro or ex vivo the efficacy of a therapeutic regimen designed to alleviate an oncogenic disorder associated with IGF-1R in a subject suffering from the disorder, the method comprising the steps of:
 (a) measuring a first expression level of IGF-1R according to the method of  claim 22  in a first biological sample, the first biological sample corresponding to the first time point of the treatment;   (b) measuring a second expression level of IGF-1R according to the method of  claim 22  in a second biological sample, the second biological sample corresponding to a second, later time point of the said treatment;   (c) calculating the ratio of the first expression level of step (a) to the second expression level of step (b); and   (d) determining that the efficacy of the therapeutic regime is high if the ratio of step (c) is greater than 1; or determining that the efficacy of the therapeutic regime is low if the ratio of step (c) is inferior or equal to 1.   
     
     
         32 . A method for selecting a cancer patient predicted to benefit or not from the administration of a therapeutic amount of an inhibitor targeting the IGF-1R pathway, the method comprising the steps of:
 (a) measuring the expression level of IGF-1R according to the method of  claim 22  in a biological sample of the patient;   (b) comparing the expression level of (a) with a reference expression level; and   (c) selecting the patient as being predicted to benefit from a treatment with an antibody drug targeting the IGF-1R pathway, if the ratio of the expression level of (a) to the said reference expression level is greater than 1; or   (d) selecting the patient as being not predicted to benefit from a treatment with an inhibitor targeting the IGF-1R pathway, if the ratio of the expression level of (a) to the reference expression level is inferior or equal to 1.   
     
     
         33 . The method of  claim 32  wherein the inhibitor is an IGF-1R antibody. 
     
     
         34 . The method of  claim 33  wherein the IGF-1R antibody is alone, combined or conjugated. 
     
     
         35 . The method of  claim 33  wherein the reference expression level is the expression level of IGF-1R in a biological sample from a healthy subject.