Augmented HER-2-specific immunity during treatment with trastuzumab and chemotherapy

Clare Taylor, Dawn Hershman, Nina Shah, Nicole Suciu-Foca, Dan P. Petrylak, Robert Taub, Linda Vahdat, Bin Cheng, Mark Pegram, Keith L Knutson, Raphael Clynes

Research output: Contribution to journalArticle

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Abstract

Purpose: 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. Experimental Design: 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 Igλ 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)5133-5143
Number of pages11
JournalClinical Cancer Research
Volume13
Issue number17
DOIs
StatePublished - Sep 1 2007

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Immunity
Drug Therapy
Neoplasm Antigens
Therapeutics
Antibodies
Active Immunity
Passive Immunization
Trastuzumab
Humoral Immunity
Cellular Immunity
Blood Cells
Research Design
Enzyme-Linked Immunosorbent Assay
Monoclonal Antibodies
T-Lymphocytes
Enzymes
Serum
Population
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Taylor, C., Hershman, D., Shah, N., Suciu-Foca, N., Petrylak, D. P., Taub, R., ... Clynes, R. (2007). Augmented HER-2-specific immunity during treatment with trastuzumab and chemotherapy. Clinical Cancer Research, 13(17), 5133-5143. https://doi.org/10.1158/1078-0432.CCR-07-0507

Augmented HER-2-specific immunity during treatment with trastuzumab and chemotherapy. / Taylor, Clare; Hershman, Dawn; Shah, Nina; Suciu-Foca, Nicole; Petrylak, Dan P.; Taub, Robert; Vahdat, Linda; Cheng, Bin; Pegram, Mark; Knutson, Keith L; Clynes, Raphael.

In: Clinical Cancer Research, Vol. 13, No. 17, 01.09.2007, p. 5133-5143.

Research output: Contribution to journalArticle

Taylor, C, Hershman, D, Shah, N, Suciu-Foca, N, Petrylak, DP, Taub, R, Vahdat, L, Cheng, B, Pegram, M, Knutson, KL & Clynes, R 2007, 'Augmented HER-2-specific immunity during treatment with trastuzumab and chemotherapy', Clinical Cancer Research, vol. 13, no. 17, pp. 5133-5143. https://doi.org/10.1158/1078-0432.CCR-07-0507
Taylor C, Hershman D, Shah N, Suciu-Foca N, Petrylak DP, Taub R et al. Augmented HER-2-specific immunity during treatment with trastuzumab and chemotherapy. Clinical Cancer Research. 2007 Sep 1;13(17):5133-5143. https://doi.org/10.1158/1078-0432.CCR-07-0507
Taylor, Clare ; Hershman, Dawn ; Shah, Nina ; Suciu-Foca, Nicole ; Petrylak, Dan P. ; Taub, Robert ; Vahdat, Linda ; Cheng, Bin ; Pegram, Mark ; Knutson, Keith L ; Clynes, Raphael. / Augmented HER-2-specific immunity during treatment with trastuzumab and chemotherapy. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 17. pp. 5133-5143.
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abstract = "Purpose: 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. Experimental Design: 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 Igλ 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. Conclusion: 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.",
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AU - Taub, Robert

AU - Vahdat, Linda

AU - Cheng, Bin

AU - Pegram, Mark

AU - Knutson, Keith L

AU - Clynes, Raphael

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N2 - Purpose: 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. Experimental Design: 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 Igλ 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. Conclusion: 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.

AB - Purpose: 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. Experimental Design: 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 Igλ 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. Conclusion: 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.

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