title: Role of immunoglobulin G fragment C receptor polymorphism-mediated antibody-dependant cellular cytotoxicity in colorectal cancer treated with cetuximab therapy.
abstract: Antibody-dependent cellular cytotoxicity (ADCC), which is activated by effector cells via immunoglobulin G (IgG) fragment C receptors (FcRs), was proposed as a mechanism of cetuximab efficacy. Peripheral blood mononuclear cells (PBMCs) from 23 healthy donors and 13 patients with metastatic colorectal cancer (mCRC) treated with cetuximab were tested for FcγR polymorphisms and cetuximab-mediated ADCC. ADCC was measured by chromium-51 release on a epidermal growth factor receptor (EGFR)-positive human colon cancer cell line. Overall, 86 mCRC patients were genotyped for study purposes. PBMCs harbouring the FcγRIIIa 158 V/V genotype had a significantly higher cetuximab-mediated ADCC. No correlation was found between FcγR polymorphisms and response rate or time to progression after cetuximab-based therapy. Despite the in vitro analysis showing that the FcγRIIIa 158 V/V genotype is associated with higher ADCC, clinical data do not support a predictive role of FcγRIIIa polymorphisms in mCRC treated with cetuximab.
authors.affiliation: Medical Oncology Unit and Medical Genetics Unit, University Hospital of Parma, Parma, Italy.
authors.forename: F V
authors.initials: FV
authors.lastname: Negri
authors.affiliation: Medical Oncology Unit and Medical Genetics Unit, University Hospital of Parma, Parma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Musolino
authors.affiliation: Medical Oncology Unit and Medical Genetics Unit, University Hospital of Parma, Parma, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Naldi
authors.affiliation: Medical Oncology Unit and Medical Genetics Unit, University Hospital of Parma, Parma, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Bortesi
authors.affiliation: Laboratory of Viral Immunopathology, Department of Infectious Diseases and Hepatology, University Hospital of Parma, Parma, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Missale
authors.affiliation: Laboratory of Viral Immunopathology, Department of Infectious Diseases and Hepatology, University Hospital of Parma, Parma, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Laccabue
authors.affiliation: Clinical Microbiology Laboratory, Department of Laboratory Medicine, Santa Maria Nuova Hospital, Reggio Emilia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Zerbini
authors.affiliation: Medical Oncology Unit and Medical Genetics Unit, University Hospital of Parma, Parma, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Camisa
authors.affiliation: Department of Radiology University Hospital of Parma, Parma, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Chernyschova
authors.affiliation: Department of Oncology, IRCCS, Santa Maria Nuova Hospital, Reggio Emilia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bisagni
authors.affiliation: Division of Medical Oncology, Department of Oncology, Transplants and New Technologies in Medicine, University of Pisa, Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Loupakis
authors.affiliation: Department of Biomolecular Sciences, University of Urbino, Urbino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ruzzo
authors.affiliation: Medical Oncology Unit and Medical Genetics Unit, University Hospital of Parma, Parma, Italy.
authors.forename: T M
authors.initials: TM
authors.lastname: Neri
authors.affiliation: Medical Oncology Unit and Medical Genetics Unit, University Hospital of Parma, Parma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ardizzoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D017452:Receptors, IgG / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C496124:FCGR3A protein, human; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D000068818:Cetuximab