title: Augmented HER-2 specific immunity during treatment with trastuzumab and chemotherapy.
abstract: OBJECTIVE
  Passive immunotherapy with antitumor antibodies has the potential to induce active tumor immunity via the opsonic enhancement of immunogenicity of tumor antigen. We have assessed whether immune sensitization to the HER-2/neu tumor antigen occurs during treatment with the anti-HER-2/neu monoclonal antibody trastuzumab.
  
  
  METHODS
  Twenty-seven patients treated with trastuzumab and chemotherapy were assessed for the induction of HER-2/neu-specific immunity. Sera and peripheral blood mononuclear cells obtained before and after trastuzumab therapy were compared for the presence of anti-HER-2/neu endogenous Iglambda antibodies and HER-2/neu-specific CD4 responses by ELISA and enzyme-linked immunospot, respectively.
  
  
  RESULTS
  Anti-HER-2/neu antibodies were detectable in 8 of 27 (29%) patients before trastuzumab treatment and in 15 of 27 (56%) patients during trastuzumab treatment. In the overall study population, anti-HER-2/neu humoral responses significantly increased during therapy (P < 0.001) and were not associated with development of an anti-idiotypic response. In 10 evaluable individuals, 6 showed augmented HER-2/neu-specific CD4 T-cell responses during therapy. Of the 22 individuals treated for metastatic disease, those patients showing objective clinical responses exhibited more frequent (P = 0.004) and larger (P = 0.006) treatment-associated anti-HER-2/neu humoral responses.
  
  
  CONCLUSIONS
  Humoral immune sensitization occurs during treatment with chemotherapy and trastuzumab. Further studies are warranted to investigate whether augmented anti-HER-2/neu humoral and cellular immunity contributes mechanistically to clinical outcome.
authors.affiliation: Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, NY 10027-6902, USA.
authors.forename: Clare
authors.initials: C
authors.lastname: Taylor
authors.forename: Dawn
authors.initials: D
authors.lastname: Hershman
authors.forename: Nina
authors.initials: N
authors.lastname: Shah
authors.forename: Nicole
authors.initials: N
authors.lastname: Suciu-Foca
authors.forename: Dan P
authors.initials: DP
authors.lastname: Petrylak
authors.forename: Robert
authors.initials: R
authors.lastname: Taub
authors.forename: Linda
authors.initials: L
authors.lastname: Vahdat
authors.forename: Bin
authors.initials: B
authors.lastname: Cheng
authors.forename: Mark
authors.initials: M
authors.lastname: Pegram
authors.forename: Keith L
authors.initials: KL
authors.lastname: Knutson
authors.forename: Raphael
authors.initials: R
authors.lastname: Clynes
mesh_terms: D000911:Antibodies, Monoclonal / Q000097:blood / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000917:Antibody Formation; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D050440:Immunoglobulin Subunits / Q000097:blood; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D000068878:Trastuzumab