Augmented HER-2 specific immunity during treatment with trastuzumab and chemotherapy.
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.
Taylor
Clare
C
Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, NY 10027-6902, USA.
Hershman
Dawn
D
Shah
Nina
N
Suciu-Foca
Nicole
N
Petrylak
Dan P
DP
Taub
Robert
R
Vahdat
Linda
L
Cheng
Bin
B
Pegram
Mark
M
Knutson
Keith L
KL
Clynes
Raphael
R
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