Methods and compositions to evaluate antibody treatment response

Abstract

The present invention relates to methods and compositions to evaluate or assess the response of a subject to particular therapeutic treatment. More particularly, the invention provides methods to determine the response of subjects, or to adapt the treatment protocol of subjects treated with therapeutic antibodies. The invention is based on a determination of the FCGR3A genotype of a subject. The invention can be used for patients with malignancies, particularly lymphoma, and is suited to select best responders and/or adjust treatment condition or protocol for low responders.

1 . A method of assessing the response of a subject to a therapeutic antibody treatment, comprising determining in vitro the FCGR3A158 genotype of said subject. 
     
     
         2 . A method of selecting patients for therapeutic antibody treatment, the method comprising determining in vitro the FCGR3A158 genotype of said subject. 
     
     
         3 . A method of improving the efficacy or treatment condition or protocol of a therapeutic antibody treatment in a subject, comprising determining in vitro the FCGR3A158 genotype of said subject. 
     
     
         4 . The method of  claim 1 , comprising determining amino acid residue at position 158 of FcγRIIIa receptor, a Valine at position 158 being indicative of a better response to said treatment and a phenylalanine at position 158 being indicative of a lower response to said treatment. 
     
     
         5 . The method of  claim 1 , wherein determining amino acid residue at position 158 of FcγRIIIa receptor comprises a step of sequencing the FcγRIIIa receptor gene or RNA or a portion thereof comprising the nucleotides encoding amino acid residue 158. 
     
     
         6 . The method of  claim 1 , wherein determining amino acid residue at position 158 of FcγRIIIa receptor comprises a step of amplifying the FcγRIIIa receptor gene or RNA or a portion thereof comprising the nucleotides encoding amino acid residue 158. 
     
     
         7 . The method of  claim 6 , wherein amplification is performed by polymerase chain reaction (PCR), such as PCR, RT-PCR and nested PCR. 
     
     
         8 . The method of  claim 1 , wherein determining amino acid residue at position 158 of FcγRIIIa receptor comprises a step of allele-specific restriction enzyme digestion. 
     
     
         9 . The method of  claim 1 , wherein determining amino acid residue at position 158 of FcγRIIIa receptor comprises a step of hybridization of the FcγRIIIa receptor gene or RNA or a portion thereof comprising the nucleotides encoding amino acid residue 158, with a nucleic acid probe specific for the genotype Valine or Phenylalanine. 
     
     
         10 . The method of  claim 1 , wherein determining amino acid residue at position 158 of FcγRIIIa receptor comprises:
 Obtaining genomic DNA from a biological sample, 
 Amplifying the FcγRIIIa receptor gene or a portion thereof comprising the nucleotides encoding amino acid residue 158, and 
 determining amino acid residue at position 158 of said FcγRIIIa receptor gene. 
 
     
     
         11 . The method of  claim 1 , wherein determining amino acid residue at position 158 of FcγRIIIa receptor comprises:
 Obtaining genomic DNA from a biological sample, 
 Amplifying the FcγRIIIa receptor gene or a portion thereof comprising the nucleotides encoding amino acid residue 158, 
 Introducing an allele-specific restriction site, 
 Digesting the nucleic acids with the enzyme specific for said restriction site and, 
 Analysing the digestion products, i.e., by electrophoresis, the presence of digestion products being indicative of the presence of the allele. 
 
     
     
         12 . The method of  claim 1 , wherein determining amino acid residue at position 158 of FcγRIIIa receptor comprises: total (or messenger) RNA extraction from cell or biological sample or biological fluid in vitro or ex vivo, optionally cDNA synthesis, (PCR) amplification with specific FCGRIIIa oligonucleotide primers, and analysis of PCR products. 
     
     
         13 . The method of  claim 1 , wherein determining amino acid residue at position 158 of FcγRIIIa receptor comprises a step of sequencing the FcγRIIIa receptor polypeptide or a portion thereof comprising amino acid residue 158. 
     
     
         14 . The method. of  claim 1 , wherein the subject is a human subject. 
     
     
         15 . The method of  claim 14 , wherein the subject has a tumor, a viral infection, or a disease condition associated with allogenic or pathological immunocompetent cells. 
     
     
         16 . The method of  claim 15 , wherein the subject has a tumor and the therapeutic antibody treatment aims at reducing the tumor burden. 
     
     
         17 . The method of  claim 16 , wherein the tumor is a lymphoma, particularly a NHL. 
     
     
         18 . The method of  claim 1 , wherein the antibody is an IgG1 or an IgG3. 
     
     
         19 . The method of  claim 18 , wherein the antibody is an anti-CD20 antibody, particularly rituximab.